Berkeley Biology 1A Spring 2016 Lecture Reader Part 1

Lecture
#1: Biology & Water
Bio 1A: Introduc/on to Biology

Spring 2016

Part I: Jennifer Doudna
Guest lecturer: Ross Wilson

Text: BIO 1A/B

UC, Berkeley
Reading: Chapters 1 & 2
Doudna oce hours
Lecture outline:
Mondays 12-1 pm
Fridays 2:30-3:30 pm
VLSB 2084
The chemistry of life

ProperTes of water are essenTal in biology
Overview:
Inquiring About the World of Life
Biology is the scienTc study of life on Earth
Evolu/on by natural selecTon is the process of
change that has produced the diverse life we
observe
Biologists ask quesTons such as:
How does a single cell develop into an organism?
How does the human brain work?
How do organisms interact in communiTes?

Dening Life
Compartmentaliza/on
Hierarchical complexity
Sensi/vity
Reproduc/on
Energy u/liza/on
Homeostasis
Adapta/on
Why Life Does Not Really Exist
h]p://Tnyurl.com/on-dening-life
Evolu/on:
the Overarching Theme of Biology
EvoluTon makes sense of everything we know
about living organisms
Organisms living on Earth are modied
descendents of common ancestors
The nature of the last universal common ancestor
(LUCA) and the origin of life represent biologys
greatest unsolved mysteries
Chemical Founda/ons of Life

Biology is a mulTdisciplinary science
Living organisms are subject to basic laws of
physics and chemistry

You should know basic deniTons of ma]er;
chemistry of water; chemistry of carbon

Elements, Compounds, Molecules
Elements, Compounds, Molecules
Ma]er is made up of elements

An element is a substance that cannot be
broken down to other substances by
chemical reacTons
A compound is a substance consisTng of
two or more elements in a xed raTo
A compound has characterisTcs dierent
from those of its elements
A molecule is two or more atoms held
together by chemical bonds
Ma]er is made up of elements

An element is a substance that cannot be
broken down to other substances by
chemical reacTons
A compound is a substance consisTng of
two or more elements in a xed raTo
A compound has characterisTcs dierent
from those of its elements
A molecule is two or more atoms held
together by chemical bonds
Is oxygen an element ? compound? molecule?
What about iron? Water? Carbon dioxide?
Salt is safer than the sum of its parts
Sodium
Chlorine
Sodium
chloride
Essen/al Elements of Life

Only about 25 of the ~80 stable elements are essenTal to life
Carbon, hydrogen, oxygen, and nitrogen make up 96% of
living ma]er
Most of the remaining 4% consists of calcium, phosphorus,
potassium, and sulfur
Trace elements are those required by an organism in minute
quanTTes
The Biochemical Periodic Table
h]p://umbbd.ethz.ch/periodic/spiral.html
Eects of Deciencies
of Essen/al Elements
Nitrogen deciency
Iodine deciency: Goiter!

The abundance of water on Earth's surface is a unique feature that
distinguishes our "Blue Planet" from others in the Solar System.
Water: The Molecule That Supports All of Life
The polarity of water molecules results in hydrogen

bonding
Water is the biological solvent on Earth

All living organisms require water more than
any other substance
Most cells are surrounded by water, and cells
themselves are about 7095% water
The abundance of water is the main reason the
Earth is habitable
The water molecule is a polar molecule:

the opposite ends have opposite charges
Polarity allows water molecules to form
hydrogen bonds with each other
Polarity also promotes interactions between
water and polar molecules or dissolved ions
Four proper/es of water contribute to Earths

tness for life
Cohesive behavior
Hydrogen
bond
Ability to moderate temperature

high specific heat
high heat of vaporization
Expansion upon freezing
Cohesion and Adhesion

Collectively, hydrogen bonds hold water
molecules together, a phenomenon called
cohesion
Versatility as a solvent
acid/base properties
dissolves many (but not all) molecules
Protons dissociate between water molecules

in a process called autoioniza/on
H+ or
Cohesion helps the transport of water against

gravity in plants
Adhesion is an attraction between different
substances, for example, between water and
plant cell walls
hydronium ion
or proton
hydroxide ion
The pH scale is logarithmic and describes the

concentra/on of hydronium ions, [H+]
NaOH Na+ & OH
Units of temperature and energy

The Celsius scale is a measure of
temperature using Celsius degrees (C)
A calorie (cal) is the amount of heat required
to raise the temperature of 1 g of water by 1C
pH = log[H+]
The Calories on food packaging are actually

kilocalories (kcal), where 1 kcal = 1,000 cal
The joule (J) is another unit of energy where
1 J = 0.239 cal
1 cal = 4.184 J
HCl H+ & Cl
Biological building blocks:

covalent connec/ons between C, H, O, N
Biological building blocks:

covalent connec/ons between C, H, O, N
available
electrons
single
bond
double
bond
N/A
Lecture #2: Biological polymers

Reading: Chapter 3
Lecture outline:
Molecular building blocks of the cell
Sugars/carbohydrates
Fats/lipids
Amino acids/proteins
Nucleo>des/nucleic acids
Overview: The Molecules of Life

All living things are made up of four classes of
large biological molecules: carbohydrates, lipids,
proteins, and nucleic acids
Within cells, small organic molecules are joined
together to form larger molecules
Building blocks of the cell:
Sugars
FaEy acids
Amino acids
Nucleo>des
Larger units of the cell:

Polysaccharides
Lipids/membranes
Proteins
Nucleic acids
Be familiar with the contents of Figure 3.2 in your book!
Carbohydrates as fuel and building material
Dehydra>on/condensa>on video:
hEp://>nyurl.com/Bio1A-vid1

Hydrolysis video:
hEp://>nyurl.com/Bio1A-vid2
Carbohydrates include sugars and the polymers of

sugars

The simplest carbohydrates are monosaccharides,
or single sugars

Carbohydrate macromolecules are
polysaccharides, polymers composed of many
sugar building blocks
Sugars
Monosaccharides have molecular formulas that
are usually mul>ples of CH2O
Glucose (C6H12O6) is the most common
monosaccharide
Monosaccharides are classied by
The loca>on of the carbonyl group (as aldose or ketose)
The number of carbons in the carbon skeleton
(pentose or hexose)
Monosaccharides serve as a major fuel for cells and
as raw material for building molecules
H
O
OH
H
C
OH
OH
HO
OH
OH
OH
H
OH
C
C2
OH
O
H
H
OH
C
H
C2
Haworth
projection
OH
CH2OH
C
H
C
OH
4
OH
C
3
-glucose
or
-glucose
Fischer
projection
H
C
OH
O
C
OH
CH2OH
O
H
C2
OH
C
1
OH
Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
H
H
O
OH
HO
H
C
OH
HO
OH
HO
OH
HO
OH
Structural
isomer
Stereoisomer
C2
OH
HO
C3
C4
OH
OH
OH
OH
C5
OH
OH
OH
OH
C6
OH
H
Fructose
H
Glucose
H
Galactose
ketose
hexose
ketohexose
aldose
hexose
aldohexose
aldose
hexose
aldohexose
Disaccharides
Polysaccharides
2 monosaccharides linked together by

dehydration synthesis
Used for sugar transport or energy storage
Examples: sucrose, lactose, maltose
CH2OH
H
HO
CH2OH
O
O H
H
OH
OH
CH2OH
H
OH
HO
H
OH
-glucose
CH2OH
HO
OH
H
Fructose
H 2O
CH2OH
O
H
OH
OH
CH2OH
O
H
O
Sucrose
OH CH OH
2
OH
H
HO
O
H
OH
OH
Long chains of monosaccharides

Linked through dehydration synthesis
Energy storage
CH2OH
H
H
O
O
H
OH
OH
H
OH
Maltose
This is an example of a condensaCon reac>on, in which two molecules

become covalently linked with the loss of a water molecule (dehydra>on).

The reverse reac>on, in which water is added, is called hydrolysis.
branched
CH2OH
H
4
HO
CH2OH
O
H
OH
CH2OH
O
H
1
OH
H
OH
-glucose
OH
OH
CH2OH
H
OH
H
OH
H
O
H
OH
H
OH
H
O
OH
OH
Starch:
H
-14 linkages
H
OH
O H
H
1
OH
CH2OH
H
CH2OH
O
H
O
Amylose
-16 linkage
CH2
O H
H
OH
OH
Glycogen
-14 linkage
unbranched
7.5 m
3.3 m
Amylopectin
Plants use starch

Animals use glycogen
Structural support
Plants use cellulose
Arthropods and fungi use chitin
The chemical formula for glucose is C6H12O6.

Whats the formula for a glycogen polymer
composed of 10 glucose molecules?
a. C60H120O60
b. C60H102O51
c. C60H100O50
d. C60H111O51
Lipids: a diverse group

of hydrophobic molecules
Lipids are the one class of large biological
molecules that do not include true polymers
The unifying feature of lipids is having liEle or no
anity for water
Lipids are hydrophobic because they consist mostly
of hydrocarbons, which form nonpolar covalent
bonds
electronega;vity:
carbon (2.5), hydrogen (2.1), oxygen (3.5)
The most biologically important lipids are fats,
phospholipids, and steroids
glycerol
Fats
Fats are constructed from two types of smaller
molecules: glycerol and faEy acids
Structural
formula of a
saturated fat
molecule
triglyceride
Stearic acid, a
saturated faNy
acid
faNy acid
Glycerol is a three-carbon alcohol with a

hydroxyl group aEached to each carbon
glycerol
Structural formula
of an unsaturated
fat molecule
A faNy acid consists of a carboxyl group

aEached to a long carbon skeleton
triglyceride
Oleic acid, an
unsaturated
faNy acid
faNy acid
cis double
bond causes
bending
Phospholipids
Hydrophilic head
Choline
Phosphate
Hydrophobic tails
Glycerol
In a phospholipid, two
faEy acids and a
phosphate group are
aEached to glycerol
The two faEy acid tails
are hydrophobic, but
the phosphate group
and its aEachments
form a hydrophilic head
FaNy acids
Hydrophilic
head
Hydrophobic
tails
Structural formula
Space-lling model
Phospholipid symbol
Phospholipids are essen>al for cells because they make up cell membranes
Steroids
Steroids are lipids characterized by a carbon
skeleton consis>ng of four fused rings
Cholesterol, an important steroid, is a
component in animal cell membranes
Although cholesterol is essen>al in animals, high
levels in the blood may contribute to
cardiovascular disease
Proteins have many structures,

resul>ng in a wide range of func>ons
Proteins account for more than 50% of the dry
mass of most cells
Protein func>ons include catalyzing biochemical
reac>ons, structural support, storage, transport,
cellular communica>ons, movement, and
defense against foreign substances
PolypepCdes are polymers built from the same
set of 20 amino acids
A protein consists of one or more polypep>des
Proteins adopt many func>ons via

combina>ons of diverse amino acids
carbon
Amino acids are organic

molecules with carboxyl
and amino groups
Amino acids dier in their
proper>es due to
diering side chains,
called R groups
Protein Structure and Func>on
PepCde
bond
A func>onal protein consists of one or more

polypep>des twisted, folded, and coiled into a
unique shape
Side chains
PepCde
bond
Groove
Backbone
Amino end
(N-terminus)
A ribbon model of lysozyme
Carboxyl end
(C-terminus)
Four Levels of Protein Structure
Examples of Quaternary Structure

Polypep>de
chain
Primary
Structure
+H N
3
Amino end
Secondary
Structure
TerCary
Structure
A space-lling model of lysozyme
Chains
Quaternary
Structure
pleated sheet
examples of
amino acid
subunits
helix
Iron
Heme
Chains
note the extensive hydrogen bonding

observed in secondary structures
Collagen
Hemoglobin
Nucleic acids store and transmit

hereditary informa>on
EXPERIMENT
Diracted
X-rays
X-ray
source X-ray
beam
Crystal
Digital detector
X-ray diracCon
paNern
RESULTS
There are two types of nucleic acids:

Deoxyribonucleic acid (DNA)
Ribonucleic acid (RNA)
The amino acid sequence of a polypep>de is

programmed by a unit of inheritance called a gene
RNA
polymerase II
DNA
Genes are stored as DNA, a nucleic acid
RNA
The Structure of Nucleic Acids
DNA
1 Synthesis of
mRNA in the
nucleus
mRNA
NUCLEUS
CYTOPLASM
mRNA
2 Movement of
mRNA into cytoplasm
via nuclear pore
Ribosome
3 Synthesis
of protein
PolypepCde
The Central Dogma

of Molecular Biology
Nucleic acids are polymers called

polynucleoCdes
Each polynucleo>de is made of monomers
called nucleoCdes
Each nucleo>de consists of a nitrogenous base,
a pentose sugar (Ribose or Deoxyribose), and a
phosphate group
The por>on of a nucleo>de without the
phosphate group is called a nucleoside
Amino
acids
Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
5 end
DNA/RNA formed via condensa>on
Nitrogenous bases
Pyrimidines
5C
NucleoCde
3C
Nucleoside
Nitrogenous
base
Cytosine (C)
Thymine (T)
in DNA
Uracil (U)
in RNA
Purines (rhymes with two rings)
Phosphate
group
5C
Sugar
(pentose)
Adenine (A)
3C
Guanine (G)
Sugars
3 end
PolynucleoCde, or nucleic acid
pentose
Deoxyribose (in DNA)
Ribose (in RNA)
Nucleoside components:
sugars and bases
The DNA Double Helix

A DNA molecule has two polynucleo>des spiraling
around an imaginary axis, forming a double helix
In the DNA double helix, the two backbones run in
opposite 5 3 direc>ons from each other, an
arrangement referred to as anCparallel
One DNA molecule includes many genes
The nitrogenous bases in DNA pair up and form
hydrogen bonds: adenine (A) always with thymine (T),
and guanine (G) always with cytosine (C)
The DNA Double Helix
5' end
3' end
Sugar-phosphate
backbones
A DNA molecule has two polynucleo>des

spiraling around an imaginary axis,
forming a double helix
In the DNA double helix, the two
backbones run in opposite 5 3
direc>ons from each other, an
arrangement referred to as anCparallel
The nitrogenous bases in DNA pair up and
form hydrogen bonds: adenine (A) always
with thymine (T), and guanine (G) always
with cytosine (C)
Base pair (joined by

hydrogen bonding)
Old strands
NucleoCde
about to be
added to a
new strand
3' end
5' end
New
strands
5' end
3' end
5' end
3' end
DNA and Proteins as Tape Measures of

Evolu>on
The linear sequences of nucleo>des in DNA
molecules are passed from parents to ospring
Two closely related species are more similar in
DNA than are more distantly related species
Molecular biology can be used to assess
evolu>onary kinship
You should now be able to:

1. List and describe the four major classes of molecules
2. Describe the forma>on of a glycosidic linkage and
dis>nguish between monosaccharides, disaccharides,
and polysaccharides
3. Dis>nguish between saturated and unsaturated fats
and between cis and trans fat molecules
4. Describe the four levels of protein structure
5. Dis>nguish between the following pairs: pyrimidine
and purine, nucleo>de and nucleoside, ribose and
deoxyribose, the 5 end and 3 end of a nucleo>de
Lecture #3: Cell structure
Reading: Chapter 4
Lecture outline:

-Methods to study cells
-Dierences between prokaryo>c and
eukaryo>c cells
-Protein tracking
-Organelles
5' end
The DNA Double

Helix
3' end
Sugar-phosphate
backbones
A DNA molecule has two polynucleo>des spiraling

around an imaginary axis, forming a double helix
In the DNA double helix, the two backbones run in
opposite 5 3 direc>ons from each other, an
arrangement referred to as anDparallel
The nitrogenous bases in DNA pair up and form
hydrogen bonds: adenine (A) always with thymine
(T), and guanine (G) always with cytosine (C)
Base pair (joined by

hydrogen bonding)
Old strands
NucleoDde
about to be
added to a
new strand
3' end
5' end
New
strands
5' end
3' end
5' end
Overview: The Fundamental Units of

Life
All organisms are made of cells
The cell is the simplest collec>on of maSer
that can live
Cell structure is correlated to cellular func>on
All cells are related by their descent from earlier
cells
3' end
How do we study cells?

Though usually too small to be seen by the unaided

eye, cells are complex
Microscopes and the tools of biochemistry have
revealed many aspects of cell biology
Microscopy
10 m
Frog egg
100 m
10 m
Most plant and

animal cells
Nucleus
Most bacteria
1 m
100 nm
10 nm
1 nm
0.1 nm
TECHNIQUE
Mitochondrion
Smallest bacteria
Viruses
Ribosomes
Electron microscope
1 mm
Unaided eye
Chicken egg
1 cm
Magnica(on, the ra>o of an objects image size to its

real size
Resolu(on, the measure of the clarity of the image, or
the minimum distance of two dis>nguishable points
Contrast, visible dierences in parts of the sample
LMs can magnify eec>vely to about 1,000 >mes

the size of the actual specimen

Various techniques enhance contrast and enable
cell components to be stained or labeled

Most subcellular structures, including organelles
(membrane-enclosed compartments), are too small
to be resolved by a LM although techniques like
uorescent labeling can make this possible by
improving contrast.
Length of some
nerve and muscle
cells
0.1 m
Scien>sts use microscopes to visualize cells too

small to see with the naked eye
In a light microscope (LM), visible light passes
through a specimen and then through glass lenses,
which magnify the image
The quality of an image depends on
Light Microscopy
Human height
Light microscope
1 m
Proteins
Lipids
Small molecules
Atoms
RESULTS
(a) BrighXield (unstained

specimen)
50 m
(b) BrighXield (stained
specimen)
Electron Microscopy
Two basic types of electron microscopes (EMs)
are used to study subcellular structures
Scanning electron microscopes (SEMs) focus a
beam of electrons onto the surface of a
specimen, providing images that look 3-D
Transmission electron microscopes (TEMs)
focus a beam of electrons through a specimen
TEMs are used mainly to study the internal
structure of cells
Scanning electron microscope image

of pollen
SEM typically provides good
depth-of-eld resolu>on, so the
surface of the sample is well
resolved.

~250 >mes beSer resolu>on
than light microscope.

Sample must be dried and
xed.

TECHNIQUE
RESULTS
(b) Transmission electron

microscopy (TEM)
1 m
Cilia
(a) Scanning electron

microscopy (SEM)
Longitudinal
secDon of
cilium
Cross secDon
of cilium
1 m
Cell Frac>ona>on
Cell fracDonaDon takes cells apart and
separates the major organelles from one
another
Ultracentrifuges frac>onate cells into their
component parts
Cell frac>ona>on enables scien>sts to
determine the func>ons of organelles
Biochemistry and cytology help correlate cell
func>on with structure
hSp://en.wikipedia.org/wiki/Microscopy
Cell fracDonaDon takes

cells apart and separates
the major organelles
from one another
Ultracentrifuges
frac>onate cells into their
component parts
Cell frac>ona>on enables
scien>sts to determine
the func>ons of
organelles
Biochemistry and
cytology help correlate
cell func>on with
structure
HomogenizaDon
Tissue
cells
1,000 g
(1,000 Dmes the
force of gravity)
10 min
Homogenate
DierenDal centrifugaDon
Supernatant poured
into next tube
20,000 g
20 min
80,000 g
60 min
Pellet rich in
nuclei and
cellular debris
150,000 g
3 hr
Pellet rich in
mitochondria
(and chloro-
plasts if cells
are from a plant)
Pellet rich in
microsomes
(pieces of plasma
membranes and
cells internal
membranes)
Basic features of all cells:
Plasma membrane
Semiuid substance called cytosol
Chromosomes (carry genes)
Ribosomes (make proteins)
No nucleus
DNA in an unbound region called the nucleoid
No membrane-bound organelles
Cytoplasm bound by the plasma membrane
1-10 m diameter
DNA in a nucleus that is bounded by a membranous nuclear envelope

Membrane-bound organelles
Cytoplasm in the region between the plasma membrane and nucleus

ENDOPLASMIC RETICULUM (ER)
Nucleoid
Flagellum
Ribosomes
Capsule
(a) A typical rodshaped
bacterium
Flagella
Rough Smooth
ER
ER
Centrosome
Plasma membrane
Cell wall
0.5 m
(b) A thin secDon

through the
bacterium Bacillus
coagulans (TEM)
proteins
EukaryoDc cells have:
Fimbriae
Bacterial
chromosome
phospholipids
The structural and func>onal unit of every organism is

one of two types of cells: prokaryo>c or eukaryo>c
Only organisms of the domains Bacteria and Archaea
consist of prokaryo>c cells
Pro>sts, fungi, animals, and plants all consist of
eukaryo>c cells
Pellet rich in
ribosomes
ProkaryoDc cells have:
Comparing Prokaryo>c and Eukaryo>c

carbohydrates
Cells
Biochemistry
TECHNIQUE
Eukaryo>c cells are

generally much larger
than prokaryo>c cells
Nuclear
envelope
Nucleolus NUCLEUS
ChromaDn
Plasma
membrane
CYTOSKELETON:
Microlaments
Intermediate
laments
Microtubules
Ribosomes
10-100 m diameter
Microvilli
Peroxisome
Mitochondrion Lysosome
Golgi
apparatus
The Nucleus: Informa>on Central

The nucleus contains most of the cells genes
and is usually the most conspicuous organelle
The nuclear envelope encloses the nucleus,
separa>ng it from the cytoplasm
The nuclear membrane is a double membrane;
each membrane consists of a lipid bilayer
Pores regulate the entry and exit of molecules
from the nucleus
The shape of the nucleus is maintained by the
nuclear lamina, which is composed of protein
Nucleus
1 m
Nucleolus
ChromaDn
Nuclear envelope:
Inner membrane
Outer membrane
Nuclear pore
Pore
complex
Surface of
nuclear envelope
Rough ER
Ribosome
1 m
0.25 m
Close-up of nuclear
envelope
Pore complexes (TEM)
Ribosomes: Protein Factories
Nuclear lamina (TEM)
Cytosol
Endoplasmic reDculum (ER)
Ribosomes are par>cles made of ribosomal RNA

and protein
Ribosomes carry out protein synthesis in two
loca>ons:
Free ribosomes
Bound ribosomes
In the cytosol (free ribosomes)

On the outside of the endoplasmic re>culum or the
nuclear envelope (bound ribosomes)
Large
subunit
0.5 m
TEM showing ER and ribosomes
Central
protuberance
Small
subunit
Structure of a ribosome
The endomembrane system regulates

protein trac and performs metabolic
func>ons in the cell
Components of the endomembrane system:
Nuclear envelope
Endoplasmic re>culum
Golgi apparatus
Lysosomes
Vacuoles
Plasma membrane
The Endoplasmic Re>culum:

Biosynthe>c Factory
The endoplasmic reDculum (ER) accounts for
more than half of the total membrane in many
eukaryo>c cells
The ER membrane is con>nuous with the
nuclear envelope
There are two dis>nct regions of ER:
Smooth ER, which lacks ribosomes
Rough ER, with ribosomes studding its surface
These components are either con>nuous or

connected via transfer by vesicles
The Golgi Apparatus: Shipping and

Receiving Center
Smooth ER
Rough ER
Nuclear
envelope
The smooth ER
Synthesizes lipids
Metabolizes
carbohydrates
Detoxies poison
Stores calcium
ER lumen
Cisternae
Ribosomes
Transport vesicle
Smooth ER
TransiDonal ER
Rough ER
200 nm
The rough ER
Has bound
ribosomes, which
secrete
glycoproteins
(proteins covalently
bonded to
carbohydrates)
Distributes transport
vesicles, proteins
surrounded by
membranes
Is a membrane
factory for the cell
The Golgi apparatus consists of aSened membranous sacs called cisternae

Func>ons of the Golgi apparatus:
Modies products of the ER

Manufactures certain macromolecules
Sorts and packages materials into transport vesicles

cis face

(receiving side of Golgi
apparatus)
Cisternae
trans face
(shipping side of Golgi
apparatus)
0.1 m
TEM of Golgi apparatus
Lysosomes: DigesDve
Compartments
Membrane tracking, vesicle transport videos:

hSps://www.youtube.com/watch?v=t7o--F02qdM

hSps://www.youtube.com/watch?v=9uA-Toy-RRA

Some types of cells

can engulf other cells
by phagocytosis; this
forms a food vacuole
A lysosome fuses
with the food
vacuole and digests
the molecules
Lysosomes also use
enzymes to recycle
the cells own
organelles and
macromolecules, a
process called
autophagy
Vesicle containing
two damaged organelles
1 m
Mitochondrion
fragment
Peroxisome
fragment
Lysosome
Peroxisome
Vesicle
Mitochondrion
DigesDon
(b) Autophagy
Mitochondria and chloroplasts convert

energy from one form to another
Mitochondria are the sites of cellular respira>on, a
metabolic process that generates ATP
Chloroplasts, found in plants and algae, are the sites of
photosynthesis
Peroxisomes are oxida>ve organelles
Mitochondria and chloroplasts
Are not part of the endomembrane system

Have a double membrane
Have proteins made by free ribosomes
Contain their own DNA
Mitochondria: Chemical Energy

Conversion
Mitochondria are in nearly all eukaryo>c cells
They have a smooth outer membrane and an
inner membrane folded into cristae
The inner membrane creates two
compartments: intermembrane space and
mitochondrial matrix
Some metabolic steps of cellular respira>on are
catalyzed in the mitochondrial matrix
Cristae present a large surface area for enzymes
that synthesize ATP
Chloroplasts: Capture of Light Energy

Intermembrane space
Outer
membrane
The chloroplast is a member of a family of plant

organelles called plasDds
Chloroplasts contain the green pigment
chlorophyll, as well as enzymes and other
molecules that func>on in photosynthesis
Chloroplasts are found in leaves and other
green organs of plants and in algae
Free ribosomes
in the
mitochondrial
matrix
Inner
membrane
Cristae
Matrix
0.1 m
Structure of a chloroplast
Peroxisomes: Oxida>on
Peroxisomes are specialized metabolic
compartments bounded by a single membrane
Peroxisomes produce hydrogen peroxide and
convert it to water
Oxygen is used to break down dierent types of
molecules
Chloroplast
Peroxisome
Mitochondrion
1 m
INTENTIONAL BLANK PAGE
Lecture #4: Cell structure pt. 2

Reading: Chapter 4
Lecture outline:
-Cytoskeleton
-Extracellular matrix
-Intercellular connec=ons
The cytoskeleton is a network of bers that

organizes structures and ac@vi@es in the cell
The cytoskeleton extends throughout the cytoplasm
It organizes the cells structures and ac=vi=es, anchoring many
organelles
It is composed of three types of molecular structures:
Microtubules
Microlaments (ac=n laments)
Intermediate laments
Microtubule
Microlaments
0.25 m
Roles of the Cytoskeleton: Support,

Mo@lity, and Regula@on
The cytoskeleton helps to support the cell and
maintain its shape
It interacts with motor proteins to produce
mo=lity
Inside the cell, vesicles can travel along
monorails provided by the cytoskeleton
Recent evidence suggests that the cytoskeleton
may help regulate biochemical ac=vi=es
ATP
(a)
Microtubule
(b)
Vesicle
Receptor for
motor protein
Motor protein
(ATP powered)
Vesicles
Microtubule
of cytoskeleton
0.25 m
Giant squid axon
Components of the Cytoskeleton

Three main types of bers make up the
cytoskeleton:
Microtubules are the thickest of the three
components of the cytoskeleton
Microlaments, also called ac=n laments, are the
thinnest components
Intermediate laments are bers with diameters in a
middle range
10 m
10 m
Column of tubulin dimers
10 m
Tubulin dimers give

rise to + and ends
of microtubules
10 m
Column of tubulin dimers
Tubulin dimer
Fibrous subunit (kera@ns

coiled together)
7 nm
10 m
Kera@n proteins
Ac@n subunit
25 nm
812 nm
Fibrous subunit (kera@ns

coiled together)
7 nm
10 m
Kera@n proteins
Ac@n subunit
25 nm
812 nm
Tubulin dimer
Movie showing microtubule forma=on/depolymeriza=on:

hQp://cryoem.berkeley.edu/movies/nogales_400x300_narrated.mov
Microtubules
Microtubules are hollow rods about 25 nm in

diameter and about 200 nm to 25 microns long
Func=ons of microtubules:
Shaping the cell
Guiding movement
of organelles
Separa=ng chromosomes
during cell division
Centrosomes and Centrioles

In many cells, microtubules grow out from a
centrosome near the nucleus
The centrosome is a microtubule-organizing
center
In animal cells, the centrosome has a pair of
centrioles, each with nine triplets of
microtubules arranged in a ring
Li H, DeRosier DJ, Nicholson WV, Nogales E,

Downing KH (2002). "Microtubule structure
at 8 resolu=on". Structure 10: 131728
Centrosome
Cilia and Flagella

Microtubule
Centrioles
0.25 m
Longitudinal sec@on of Microtubules

one centriole
Cross sec@on
of the other centriole
Microtubules control the bea=ng of cilia and

agella, locomotor appendages of some cells
Cilia and agella share a common
ultrastructure:
A core of microtubules sheathed by the plasma
membrane (9 doublets arranged in a ring @ 2
singlets see p. 115)
A basal body that anchors the cilium or agellum
A motor protein called dynein, which drives the
bending movements of a cilium or agellum
Direc@on of swimming
(a) Mo@on of agella
5 m
Movie showing dynein walking along microtubule

hQps://www.youtube.com/watch?v=JX2MdZX6Bys
Direc@on of organisms movement
Power stroke
Recovery stroke
(b) Mo@on of cilia
15 m
Microtubule
doublets
ATP
How dynein walking

moves agella and cilia:
Dynein arms alternately

grab, move, and release
the outer microtubules
Protein cross-links limit
sliding
Forces exerted by dynein
arms cause doublets to
curve, bending the cilium
or agellum
Microvillus
Plasma membrane
Dynein
protein
(a) Eect of unrestrained dynein movement

ATP
Cross-linking proteins
inside outer doublets
Microlaments (ac@n
laments)
Anchorage
in cell
(b) Eect of cross-linking proteins

1
3
2
(c) Wavelike mo@on
Intermediate laments
0.25 m
Microlaments are solid

rods about 7 nm in
diameter, built as a
twisted double chain of
ac@n subunits
The structural role of
microlaments is to bear
tension, resis=ng pulling
forces within the cell
They form a 3-D network
called the cortex just
inside the plasma
membrane to help
support the cells shape
Bundles of
microlaments make up
the core of microvilli of
intes=nal cells
Microlaments that func=on in cellular mo=lity

contain the protein myosin in addi=on to ac=n
In muscle cells, thousands of ac=n laments are
arranged parallel to one another
Thicker laments composed of myosin
interdigitate with the thinner ac=n bers
Muscle cell
Ac@n lament
Myosin lament
Myosin arm
(a) Myosin motors in muscle cell contrac@on
Intermediate Filaments
Intermediate laments range in diameter from
812 nanometers, larger than microlaments
but smaller than microtubules
They support cell shape and x organelles in
place
Intermediate laments are more permanent
cytoskeleton xtures than the other two classes
Extracellular components help

coordinate cellular ac=vi=es
Most cells synthesize and secrete materials that
are external to the plasma membrane
These extracellular structures include:
Cell walls of plants
The extracellular matrix (ECM) of animal cells
Intercellular junc=ons
Cell Walls of Plants

The cell wall is an extracellular structure that
dis=nguishes plant cells from animal cells
Prokaryotes, fungi, and some pro=sts also have
cell walls
The cell wall protects the plant cell, maintains its
shape, and prevents excessive uptake of water
Plant cell walls are made of cellulose bers
embedded in other polysaccharides and protein
Plant cell walls may

have mul=ple layers:
Secondary
cell wall
Primary cell
wall
Primary cell wall:

rela=vely thin and
exible
Middle lamella:
thin layer between
primary walls of
adjacent cells
Secondary cell wall
(in some cells):
added between the
plasma membrane
and the primary cell
wall
Middle
lamella
1 m
Central vacuole
Cytosol
Plasma membrane
Plasmodesmata are
channels between
adjacent plant cells
Plant cell walls
Plasmodesmata
The Extracellular Matrix (ECM) of

Animal Cells
Animal cells lack cell walls but are covered by an
elaborate extracellular matrix (ECM)
The ECM is made up of glycoproteins such as
collagen, proteoglycans, and bronec@n
ECM proteins bind to receptor proteins in the
plasma membrane called integrins
Func=ons of the ECM:

Support
Adhesion
Movement
Regula=on
Collagen
Proteoglycan
complex
EXTRACELLULAR FLUID
Polysaccharide
molecule
Carbo-
hydrates
Fibronec@n
Core
protein
Integrins
Proteoglycan
molecule
Plasma
membrane
Proteoglycan complex
Micro-
laments
CYTOPLASM
Intercellular Junc=ons
Plasmodesmata in Plant Cells

Plasmodesmata are channels that perforate plant cell
walls
Through plasmodesmata, water and small solutes (and
some=mes proteins and RNA) can pass from cell to cell
Neighboring cells in =ssues, organs, or organ systems

oren adhere, interact, and communicate through
direct physical contact
Intercellular junc=ons facilitate this contact
There are several types of intercellular junc=ons
Plasmodesmata
Tight junc=ons
Desmosomes
Gap junc=ons
Cell walls
Interior
of cell
Interior
of cell
0.5 m
Tight Junc;ons,
Desmosomes, and
Gap Junc;ons in
Animal Cells
Tight junc@on
Tight junc@ons prevent
uid from moving
across a layer of cells
Cells rely on the integra=on of structures and

organelles in order to func=on
Intermediate
laments
Desmosome
Desmosome
Gap
junc@ons
Space
between
cells
Plasma membranes
of adjacent cells
Extracellular
matrix
1 m
Gap junc@on
0.1 m
5 m
At @ght junc@ons,
membranes of neighboring
cells are pressed together,
preven=ng leakage of
extracellular uid
Desmosomes (anchoring
junc=ons) fasten cells
together into strong sheets
Gap junc@ons
(communica=ng junc=ons)
provide cytoplasmic
channels between adjacent
cells
Plasma membranes
The Cell: A Living Unit Greater Than the

Sum of Its Parts
0.5 m
Tight junc@on
Plasmodesmata
For example, a
macrophages ability to
destroy bacteria
involves the whole cell,
coordina=ng
components such as the
cytoskeleton,
lysosomes, and plasma
membrane
SUMMARY
SUMMARY
Cell Component
Concept 6.3
The eukaryo@c cells gene@c
instruc@ons are housed in
the nucleus and carried out
by the ribosomes
Structure
Nucleus
Func@on
Surrounded by nuclear
envelope (double membrane)
perforated by nuclear pores.
The nuclear envelope is
con@nuous with the
endoplasmic re@culum (ER).
Houses chromosomes, made of

chroma@n (DNA, the gene@c
material, and proteins); contains
nucleoli, where ribosomal
subunits are made. Pores
regulate entry and exit of
materials.
Two subunits made of ribo-

somal RNA and proteins; can be
free in cytosol or bound to ER
Protein synthesis
Extensive network of
membrane-bound tubules and
sacs; membrane separates
lumen from cytosol;
con@nuous with
the nuclear envelope.
Smooth ER: synthesis of

lipids, metabolism of carbohy-
drates, Ca2+ storage, detoxica-@on
of drugs and poisons
(ER)
Ribosome
Concept 6.4
The endomembrane system
regulates protein trac and
performs metabolic func@ons
in the cell
Concept 6.5
Mitochondria and chloro-
plasts change energy from
one form to another
Endoplasmic re@culum
(Nuclear
envelope)
Stacks of alened
membranous
sacs; has polarity
(cis and trans
faces)
Lysosome
Membranous sac of hydroly@c

enzymes (in animal cells)
Vacuole
Large membrane-bounded
vesicle in plants
Mitochondrion
Bounded by double
membrane;
inner membrane has
infoldings (cristae)
Typically two membranes

around uid stroma, which
contains membranous thylakoids
stacked into grana (in plants)
Chloroplast
Specialized metabolic
compartment bounded by a
single membrane
Peroxisome
Concept 6.3
The eukaryo@c cells gene@c
instruc@ons are housed in
the nucleus and carried out
by the ribosomes
Modica@on of proteins, carbo-

hydrates on proteins, and phos-
pholipids; synthesis of many
polysaccharides; sor@ng of Golgi
products, which are then
released in vesicles.
Golgi apparatus
Nucleus
Breakdown of ingested substances,

cell macromolecules, and damaged
organelles for recycling
Func@on
Surrounded by nuclear
envelope (double membrane)
perforated by nuclear pores.
The nuclear envelope is
con@nuous with the
endoplasmic re@culum (ER).
Houses chromosomes, made of

chroma@n (DNA, the gene@c
material, and proteins); contains
nucleoli, where ribosomal
subunits are made. Pores
regulate entry and exit os
materials.
Two subunits made of ribo-

somal RNA and proteins; can be
free in cytosol or bound to ER
Protein synthesis
(ER)
Diges@on, storage, waste

disposal, water balance, cell
growth, and protec@on
Ribosome
Cellular respira@on
Photosynthesis
Contains enzymes that transfer

hydrogen to water, producing
hydrogen peroxide (H2O2) as a
by-product, which is converted
to water by other enzymes
in the peroxisome
SUMMARY
SUMMARY
Cell Component
Concept 6.4
The endomembrane system
regulates protein trac and
performs metabolic func@ons
in the cell
Structure
Cell Component
Rough ER: Aids in synthesis of

secretory and other proteins from
bound ribosomes; adds
carbohydrates to glycoproteins;
produces new membrane
Structure
Extensive network of
membrane-bound tubules and
(Nuclear sacs; membrane separates
envelope)
lumen from cytosol;
con@nuous with
the nuclear envelope.
Endoplasmic re@culum
Golgi apparatus
Lysosome
Vacuole
Stacks of alened
membranous
sacs; has polarity
(cis and trans
faces)
Membranous sac of hydroly@c

enzymes (in animal cells)
Large membrane-bounded
vesicle in plants
Func@on
Smooth ER: synthesis of
lipids, metabolism of carbohy-
drates, Ca2+ storage, detoxica-
@on of drugs and poisons
Rough ER: Aids in sythesis of
secretory and other proteins
from bound ribosomes; adds
carbohydrates to glycoproteins;
produces new membrane
Modica@on of proteins, carbo-
hydrates on proteins, and phos-
pholipids; synthesis of many
polysaccharides; sor@ng of
Golgi products, which are then
released in vesicles.
Breakdown of ingested sub-
stances cell macromolecules, and
damaged organelles for recycling
Diges@on, storage, waste
disposal, water balance, cell
growth, and protec@on
Cell Component
Concept 6.5
Mitochondrion
Mitochondria and chloro-

plasts change energy from
one form to another
Structure
Bounded by double
membrane;
inner membrane has
infoldings (cristae)
Func@on
Cellular respira@on
Chloroplast
Typically two membranes

around uid stroma, which
contains membranous thylakoids
stacked into grana (in plants)
Photosynthesis
Peroxisome
Specialized metabolic
compartment bounded by a
single membrane
Contains enzymes that transfer

hydrogen to water, producing
hydrogen peroxide (H2O2) as a
by-product, which is converted
to water by other enzymes
in the peroxisome
Based on lectures 3 & 4, you should

now be able to:
1. Dis=nguish between the following pairs of
terms: prokaryo=c and eukaryo=c cell; free
and bound ribosomes; smooth and rough ER
2. Describe the structure and func=on of the
components of the endomembrane system
3. Briey explain the role of mitochondria,
chloroplasts, and peroxisomes
4. Describe the func=ons of the cytoskeleton
5. Compare the structures and func=ons of

microtubules, microlaments, and
intermediate laments
6. Explain how the ultrastructure of cilia and
agella relate to their func=ons
7. Describe the structure of a plant cell wall
8. Describe the structure and roles of the
extracellular matrix in animal cells
9. Describe four dierent intercellular junc=ons
Lecture #5: Biological membranes

Reading: Chapter 5
Lecture outline: Membrane structure and
func:on
Overview: Life at the Edge

The plasma membrane is the boundary that
separates the living cell from its surroundings
The plasma membrane exhibits selec5ve
permeability, allowing some substances to
cross it more easily than others
Fluid mosaic model

Membrane proteins
Osmosis
Ac:ve transport
Cellular membranes are uid

mosaics of lipids and proteins
Phospholipids are the most abundant lipid in the
plasma membrane
Phospholipids are amphipathic molecules,
containing hydrophobic and hydrophilic regions
The uid mosaic model states that a membrane is
a uid structure with a mosaic of various
proteins embedded in it
Hydrophilic
head
WATER
Hydrophobic
tail
Fluid mosaic model of membrane

structure
Phospholipid
bilayer
Hydrophobic regions
of protein
WATER
Hydrophilic
regions of protein
Freeze-fracture experiments
Freeze-fracture studies of the plasma membrane supported the uid
mosaic model
Freeze-fracture is a specialized prepara:on technique that splits a
membrane along the middle of the phospholipid bilayer
Fluid mosaic video

hIps://www.youtube.com/watch?v=Qqsf_UJcfBc
TECHNIQUE
RESULTS
Extracellular
layer
Proteins
Knife
Plasma membrane
Inside of extracellular layer
Cytoplasmic layer
Inside of cytoplasmic layer
Freeze fracture electron microscopy
The Fluidity of
Membranes
Lateral movement
(~107 times per second)
Phospholipids in the
plasma membrane can
move within the bilayer
Most of the lipids, and
some proteins, dri_
laterally
Rarely does a molecule
ip-op transversely
across the membrane
Flip-flop
(~ once per month)
(a) Movement of phospholipids

Fluid
Unsaturated hydrocarbon
tails with kinks
Viscous
Saturated hydrocarbon tails
(b) Membrane fluidity
Cholesterol
A. Fujita, J. Cheng & T. Fujimoto

Nature Protocols 5, 661 - 669 (2010)

(c) Cholesterol within the animal cell membrane
Experiment: are membranes uid?

RESULTS
Membrane proteins
Mouse cell
Mixed proteins
after 1 hour
Human cell
Hybrid cell
Frye and Edidin (1970) The rapid intermixing of cell surface an:gens a_er forma:on
of mouse-human heterokaryons. Journal of Cell Science 7:319.
Membrane Proteins and Their Func5ons

Peripheral proteins are bound to the surface of
the membrane
Integral proteins penetrate the hydrophobic
core
Integral proteins that span the membrane are
called transmembrane proteins
The hydrophobic regions of an integral protein
consist of one or more stretches of nonpolar
amino acids, o_en coiled into alpha helices
Are integral membrane proteins amphipathic?
Six major func:ons of membrane

proteins:
Transport

Enzyma:c ac:vity
EXTRACELLULAR
N-terminus
GPCR video:
hIps://www.youtube.com/watch?v=2r0GyTEimZM
Signal transduc:on
Cell-cell
recogni:on
Intercellular joining
AIachment to the
cytoskeleton and
extracellular matrix
(ECM)
SIDE
C-terminus
Helix
CYTOPLASMIC
SIDE
Signaling molecule
Enzymes
ATP
(a) Transport
Receptor
Signal transduction
(b) Enzymatic activity
(c) Signal transduction
(e) Intercellular joining
(f) Attachment to
the cytoskeleton
and extracellular
matrix (ECM) i.e. HIV co-receptor
Glycoprotein
(d) Cell-cell recognition
Blood types
Synthesis and Sidedness of Membranes

Membranes have dis:nct inside and outside
faces
The asymmetrical distribu:on of proteins, lipids,
and associated carbohydrates in the plasma
membrane is determined when the membrane
is built by the ER and Golgi apparatus
Synthesis and
Sidedness of
Membranes
Membranes have
dis:nct inside and
outside faces
The asymmetrical
distribu:on of proteins,
lipids, and associated
carbohydrates in the
plasma membrane is
determined when the
membrane is built by
the ER and Golgi
apparatus
ER
Transmembrane
glycoproteins
Secretory
protein
Glycolipid
Golgi
2
apparatus
Vesicle
4
Secreted
protein
Plasma membrane:
Cytoplasmic face
Extracellular face
Transmembrane
glycoprotein
Membrane glycolipid
Membrane structure results in

selec5ve permeability
A cell must exchange materials with its
surroundings, a process controlled by the
plasma membrane
Plasma membranes are selec:vely permeable,
regula:ng the cells molecular trac
Hydrophobic (nonpolar) molecules, such as
hydrocarbons, can dissolve in the lipid bilayer
and pass through the membrane rapidly
Polar molecules, such as sugars, do not cross
the membrane easily
Molecules of dye
WATER
Net diffusion
Equilibrium
(a) Diffusion of one solute
Net diffusion
Net diffusion
(b) Diffusion of two solutes
Net diffusion
Net diffusion
Diusion is the tendency for molecules to

spread out evenly into the available space
Although each molecule moves randomly,
diusion of a popula:on of molecules may
exhibit a net movement in one direc:on
At dynamic equilibrium, as many molecules
cross one way as cross in the other direc:on
Eects of Osmosis on Water Balance
Membrane (cross section)
Net diffusion
Passive transport: diusion across a

membrane with no energy investment
Equilibrium
Equilibrium
Osmosis is the diusion of water across a

selec:vely permeable membrane
Water diuses across a membrane from the
region of lower solute concentra:on to the
region of higher solute concentra:on
Higher
concentration
of sugar
Lower
concentration
of solute (sugar)
Water Balance of Cells Without Walls
Same concentration
of sugar
Tonicity is the ability of a solu:on to cause a cell

to gain or lose water
Isotonic solu:on: Solute concentra:on is the
same as that inside the cell; no net water
movement across the plasma membrane
Hypertonic solu:on: Solute concentra:on is
greater than that inside the cell; cell loses water
Hypotonic solu:on: Solute concentra:on is less
than that inside the cell; cell gains water
H 2O
Selectively
permeable
membrane
Osmosis
Hypotonic solution
H 2O
Isotonic solution
Hypertonic solution
H 2O
H 2O
H 2O
(a) Animal
cell
Lysed
H 2O
Normal
H 2O
Shriveled
H 2O
H 2O
(b) Plant
cell
Turgid (normal)
Flaccid
Plasmolyzed
Transport Proteins
Transport proteins allow passage of hydrophilic
substances across the membrane
Some transport proteins, called channel
proteins, have a hydrophilic channel that certain
molecules or ions can use as a tunnel
Channel proteins called aquaporins facilitate
the passage of water
Facilitated Diusion: Passive Transport

Aided by Proteins
EXTRACELLULAR
FLUID
In facilitated diusion, transport proteins speed

the passive movement of molecules across the
plasma membrane
Channel protein
Solute
CYTOPLASM
Channel proteins provide corridors that allow a

specic molecule or ion to cross the membrane
Channel proteins include
(a) A channel protein
Aquaporins, for facilitated diusion of water

Ion channels that open or close in response to a
s:mulus (gated channels)
Solute
Carrier protein
(b) A carrier protein
Ac5ve transport uses energy to move

solutes against their gradients
Facilitated diusion is s:ll passive because the
solute moves down its concentra:on gradient
Some transport proteins, however, can move
solutes against their concentra:on gradients
Ac5ve transport moves substances against their
concentra:on gradient
Ac:ve transport requires energy, usually in the
form of ATP
Ac:ve transport is performed by specic
proteins embedded in the membranes
EXTRACELLULAR
FLUID
[Na+] high
[K+] low
Na+
Na+
Na+
Na+
Na+
Na+
Na+
Na+
CYTOPLASM
Na+
[Na+] low
[K+] high
P
ADP
ATP
K+
K+
K+
K+
K+
K+
Ion Pumps Maintain Membrane Poten5al

Membrane poten5al is the voltage dierence
across a membrane (inside of cell is nega:vely
charged)
Voltage is created by dierences in the distribu:on
of posi:ve and nega:ve ions
An electrogenic pump is a transport protein

that generates voltage across a membrane
The sodium-potassium pump is the major
electrogenic pump of animal cells
The main electrogenic pump of plants, fungi,
and bacteria is a proton pump
Two combined forces, collec:vely called the

electrochemical gradient, drive the diusion of
ions across a membrane:
A chemical force (the ions concentra:on gradient)
An electrical force (the eect of the membrane
poten:al on the ions movement)
ATP
H+
H+
+
Proton pump
H+
H+
H+
+
Sucrose-H+
H+
H+ Diffusion
of H+
cotransporter
H+
Sucrose
+
+
Sucrose
Bulk transport by exocytosis and

endocytosis
Small molecules and water enter or leave the cell
through the lipid bilayer or by transport proteins
Large molecules, such as polysaccharides and
proteins, cross the membrane in bulk via vesicles
Bulk transport requires energy
In exocytosis, transport vesicles migrate to the
membrane, fuse with it, and release their contents
In endocytosis, the cell takes in macromolecules by
forming vesicles from the plasma membrane

SUMMARY
PHAGOCYTOSIS
EXTRACELLULAR
FLUID
Passive transport
1 m
CYTOPLASM
Active transport
Pseudopodium
Pseudopodium
of amoeba
Foodor
other particle
Bacterium
Food
vacuole
Food vacuole
An amoeba engulfing a bacterium
via phagocytosis (TEM)
PINOCYTOSIS
0.5 m
Plasma
membrane
Pinocytosis vesicles
forming (arrows) in
a cell lining a small
blood vessel (TEM)
Vesicle
RECEPTOR-MEDIATED ENDOCYTOSIS
Coat protein
Receptor
Coated
vesicle
ATP
Diffusion
Facilitated diffusion
Coated
pit
Ligand
A coated pit
and a coated
vesicle formed
during
receptormediated
endocytosis
(TEMs)
Coat
protein
Plasma
membrane
0.25 m

1. Dene the following terms: amphipathic
molecules, aquaporins, diusion
2. Explain how membrane uidity is inuenced
by temperature and membrane composi:on
3. Dis:nguish between the following pairs or sets
of terms: peripheral and integral membrane
proteins; channel and carrier proteins;
osmosis, facilitated diusion, and ac:ve
transport; hypertonic, hypotonic, and isotonic
solu:ons
4. Explain how transport proteins facilitate

diusion
5. Explain how an electrogenic pump creates
voltage across a membrane, and name two
electrogenic pumps
6. Explain how large molecules are transported
across a cell membrane
Overview: The Energy of Life
Lecture #6: Cellular metabolism

Reading: Chapter 6
Lecture outline: Why we need enzymes
Metabolic pathways
Thermodynamics
Free energy
Introduc@on to enzymes
An organisms metabolism transforms ma?er and

energy, subject to the laws of thermodynamics
Metabolism is the totality of an organisms

chemical reac@ons
Metabolism is an emergent property of life that
arises from interac@ons between molecules
within the cell
The living cell is a miniature chemical factory

where thousands of reac@ons occur
The cell extracts energy and applies energy to
perform work
Some organisms even convert energy to light, as
in bioluminescence
OrganizaEon of the Chemistry of Life

into Metabolic Pathways
A metabolic pathway begins with a specic
molecule and ends with a product
Each step is catalyzed by a specic enzyme
Enzyme 1
Metabolomics:
the study of all the small molecules metabolites in a cell
Reaction 1
Starting
molecule
Enzyme 2
B
Reaction 2
Enzyme 3
C
Reaction 3
Product
Some metabolic pathways break down

molecules
Catabolic pathways release energy by breaking
down complex molecules into simpler
compounds
Cellular respira@on, the breakdown of glucose in
the presence of oxygen, is an example of a
pathway of catabolism
And some metabolic pathways create

molecules
Anabolic pathways consume energy to build
complex molecules from simpler ones
The synthesis of protein from amino acids is an
example of anabolism
BioenergeEcs is the study of how organisms
manage their energy resources
Energy is the capacity to do work

Energy exists in various forms, some of which can
perform work:
KineEc energy is energy associated with mo@on
Heat (thermal energy) is kine@c energy associated with
random movement of atoms or molecules
PotenEal energy is energy that maLer possesses
because of its loca@on or structure
Chemical energy is poten@al energy available for
release in a chemical reac@on
Energy can be converted from one form to another
A diver has more potential

energy on the platform
than in the water.
Diving converts
potential energy to
kinetic energy.
The Laws of Energy Transforma@on

Thermodynamics is the study of energy
transforma@ons
A closed system, such as that approximated by
liquid in a thermos, is isolated from its
surroundings
In an open system, energy and maLer can be
transferred between the system and its
surroundings
Organisms are open systems
Climbing up converts the kinetic

energy of muscle movement
to potential energy.
A diver has less potential

energy in the water
than on the platform.
The First Law of Thermodynamics

According to the rst law of thermodynamics,
the energy of the universe is constant:
Energy can be transferred and transformed, but it
cannot be created or destroyed
The rst law is also called the principle of

conserva@on of energy
Two laws of thermodynamics govern energy transforma@ons in organisms

and other collec@ons of maLer
The Second Law of Thermodynamics

During every energy transfer or transforma@on,
some energy is unusable, and is oPen lost as
heat
According to the second law of
thermodynamics:
Every energy transfer or transforma<on increases
the entropy (disorder) of the universe

Heat
Where does the energy that supports life come from?
Chemical
energy
(a) First law of thermodynamics
CO2
+
H 2O
(b) Second law of thermodynamics
Biological Order and Disorder

Living cells unavoidably convert organized forms
of energy to heat
Spontaneous processes occur without energy
input; they can happen quickly or slowly
For a process to occur without energy input, it
must increase the entropy of the universe (S is
posi@ve) or its total energy must decrease (H is
nega@ve)
Cells create ordered

structures from less ordered
materials
Organisms also replace
ordered forms of maLer and
energy with less ordered
forms
Energy ows into an
ecosystem in the form of
light and exits in the form of
heat
G = H - TS
Why does the evolu@on of more complex

organisms not violate the second law of
thermodynamics?
Entropy (disorder) may decrease in an

organism (an open system), but the
universes total entropy increases

Equilibrium and Metabolism

Reactions in a closed system eventually reach
equilibrium and then do no work
Cells are not in equilibrium; they are open systems
experiencing a constant flow of materials
A defining feature of life is that metabolism is
never at equilibrium
A catabolic pathway in a cell releases free energy
in a series of reactions
Free-Energy Change, G
The change in free energy (G) during a
process is related to the change in enthalpy,
or change in total energy (H), change in
entropy (S), and temperature in Kelvin (T):
G = H TS
Only processes with a negative G are
spontaneous
Spontaneous processes can be harnessed
to perform work
The free-energy change of a

reaction tells whether or not the
reaction occurs spontaneously
Biologists want to know which reactions
occur spontaneously and which require
input of energy
To do so, they need to determine energy
changes that occur in chemical reactions
A living systems free energy is energy that
is available to do work when temperature
and pressure are uniform, as in a living cell
Reaction coordinate diagram

Free energy, G, is plotted
as a function of the reaction
progress (the reaction coordinate).
The starting point for the forward
or reverse reaction is called the
ground state.
The free energy change
that occurs during a reaction under
a standard set of conditions
(temperature 298 K; 1 atm pressure;
1 M solute concentrations) is denoted
G. G is the standard free-energy
change at pH 7.
(and remember the change in Gibbs
free energy relationship: G = H - TS)
Enzymes
Free Energy, Stability, and Equilibrium

Free energy is a measure of a systems
instability, its tendency to change to a more
stable state
During a spontaneous change, free energy
decreases and the stability of a system
increases
Equilibrium is a state of maximum stability
A process is spontaneous and can perform
work only when it is moving toward
equilibrium
Enzymes (in yeast) are the chemical reaction

catalysts of biological systems.
Most enzymes are proteins, and they often use metal
ions or prosthetic groups like vitamins to assist catalysis.
Many inherited genetic disorders result from a defect
or even a total absence of a particular enzyme, or
excessive activity of an enzyme.
Measurement of enzyme activities in body fluids is
important in diagnosing various illnesses. Furthermore,
many drugs act by altering the activities of
enzymes. And enzymes are practical tools in the laboratory.
Lactose intolerance
People lacking the enzyme lactase cant digest a sugar
found in milk/dairy products:
Video about enzymes

https://www.youtube.com/watch?v=E2UNc5zBejc
Lactose:
Whats the cause of lactose intolerance?

How is lactose intolerance treated?
Discovery of enzymes
In 1897 it was discovered that yeast extracts

could ferment sugar to alcohol:
In 1926, jack bean urease was isolated and

crystallized. This enzyme catalyzes the
reaction:
C6H12O6 2C2H5OH + 2CO2 + 2 ATP
CH4N2O + H2O 2NH3 + CO2
This finding showed that fermentation was

promoted by molecules that continued to
function when removed from cells.
The urease crystals contained only protein,

leading to the idea that all enzymes
are proteins.
Various intestinal-tract pathogens produce urease, enabling detection of urease to be
used as a diagnostic. For example: Helicobacter pylori, which causes ulcers.
In 1926, jack bean urease was isolated and
crystallized. This enzyme catalyzes the
reaction:
CH4N2O + H2O 2NH3 + CO2
The urease crystals contained only protein,
leading to the idea that all most enzymes
are proteins.
In the 1930s, weak chemical bonding
interactions between an enzyme and
its substrate were hypothesized be used to
catalyze a reaction.
This key insight lies at the heart of our current
understanding of enzyme catalysis.
Enzymes speed up the rates of

biochemical reactions
Some examples of enzyme-catalyzed rate

enhancements
The active site of an enzyme is usually

a cleft or pocket where chemistry takes place.
A molecule that binds in the active site and
is acted upon by the enzyme is called
a substrate.
As simple equation for an enzyme-catalyzed
reaction can be written:
E + S D ES D EP D E + P
where E is enzyme, S is substrate and P is product.
Enzymes do not alter the reaction equilibrium, but
they alter the forward and reverse reaction rates.
Enzymes remain unchanged after the reaction.
Comparison of catalyzed vs.

uncatalyzed reaction
Note that enzyme names typically end in ase
Free energy and equilibrium

constant are related
Keq = [P]/[S]
The activation energy of the reaction

is lower when catalyzed by an
enzyme.
One idea about how enzymes work
is that they bind to the transition
state better than to the substrate
or product, stabilizing the
transition state.
From thermodynamics, the equilibrium

constant and the free energy are related
by the expression
G = -RTln Keq
= -2.3RTlog Keq
If the equilibrium constant is 1, the energy
released is zero. If the equilibrium constant
is 1000, then the free energy released
is -17 kJ/mole.
Binding energy, GB, is a major source of free energy used by enzymes to lower
the activation energy of a reaction.
Lecture #7: Enzyme func1on
G = H - TS
Free energy
Enzyme-catalyzed reac?ons
ATP powers much of the cells work
Spontaneous processes occur without energy

input; they can happen quickly or slowly

For a process to occur without energy input, it
must increase the entropy of the universe (S is
posi?ve) or its total energy (enthalpy) must
decrease (H is nega?ve)
Enzymes speed up the rates of biochemical

reac1ons
Enzymes speed up metabolic reac1ons

by lowering energy barriers
Reading: Chapter 6
Lecture outline: How enzymes work
The ac1ve site of an enzyme is usually

a cleM or pocket where chemistry takes place.

A molecule that binds in the ac?ve site and
is acted upon by the enzyme is called
a substrate.

As simple equa?on for an enzyme-catalyzed
reac?on can be wriPen:


where E is enzyme, S is substrate and P is product.

Enzymes do not alter the reac?on equilibrium, but
they alter the forward and reverse reac?on rates.

Enzymes remain unchanged aMer the reac?on.
A catalyst is a chemical agent that speeds up a

reac?on without being consumed by the
reac?on
An enzyme is a cataly?c protein
Hydrolysis of sucrose by the enzyme sucrase is
an example of an enzyme-catalyzed reac?on
The Ac1va1on Energy Barrier

Every chemical reac?on between molecules
involves bond breaking and bond forming
The ini?al energy needed to start a chemical
reac?on is called the free energy of ac1va1on,
or ac1va1on energy (EA)
Ac?va?on energy is oMen supplied in the form
of heat from the surroundings
Sucrose (C12H22O11)
Sucrase
Glucose (C6H12O6)
Fructose (C6H12O6)
How Enzymes Lower the EA Barrier

Enzymes catalyze reac?ons by lowering the EA
barrier
Enzymes do not aect the change in free energy
(G); instead, they increase the reac?on rate
Free energy
Transition state
EA
Reactants
A
G < O
Products
Progress of the reaction
Free energy
Course of
reaction
without
enzyme
EA
without
enzyme
EA with
enzyme
is lower
Reactants
Course of
reaction
with enzyme
G is unaffected
by enzyme
Products
Binding energy, GB, is a major source of free energy used by enzymes to lower
the ac?va?on energy of a reac?on.
Progress of the reaction

Substrate Specicity of Enzymes

The reactant that an enzyme acts on is called
the enzymes substrate
The enzyme binds to its substrate, forming an
enzyme-substrate complex
The ac1ve site is the region on the enzyme
where the substrate binds
Induced t of a substrate brings chemical
groups of the ac?ve site into posi?ons that
enhance their ability to catalyze the reac?on
Substrate
Active site
Enzyme
(a)
Enzyme-substrate
complex
(b)
Catalysis in the Enzymes Ac?ve Site
Video on hexokinase:
hPps://www.youtube.com/watch?v=2gZDHMQcgtQ
In an enzyma?c reac?on, the substrate binds to

the ac?ve site of the enzyme
The ac?ve site can lower an EA barrier by
Orien?ng substrates correctly
Straining substrate bonds
Providing a favorable microenvironment
Covalently bonding to the substrate
Enzymes bind beLer to transi1on states than to

substrates
Chorismate mutase example:

hPp://en.wikipedia.org/wiki/Chorismate_mutase

hPp://en.wikipedia.org/wiki/Chorismate_mutase#mediaviewer/
File:Chorismate_Mutase_Scheme.png

hPp://www.pnas.org/content/111/49/17516.abstract

hPp://www.pnas.org/content/95/25/14640/F2.large.jpg
Transi1on state analogs mimic the

structure in the transi1on state
An1bodies that bind to transi1on state

analogs can some1mes be catalysts
The Hilvert Lab

hPp://www.protein.ethz.ch
Binding energy contributes to catalysis in

mul1ple ways:
1 Substrates enter active site; enzyme

changes shape such that its active site 2 Substrates held in
active site by weak
enfolds the substrates (induced fit).
interactions, such as
hydrogen bonds and
ionic bonds.
Substrates
Enzyme-substrate
complex
Entropy reduc?on
Substrate desolva?on
6
Active
site is
available
for two new
substrate
molecules.
3 Active site can lower EA

and speed up a reaction.
Enzyme
Induced t
Products
5
are
released.
Products
4 Substrates are
converted to
products.
Eects of Local Condi?ons on Enzyme

Ac?vity
Specic cataly1c groups contribute to catalysis
An enzymes ac?vity can be aected by
General acid-base
catalysis
General environmental factors, such as temperature

and pH
Chemicals that specically inuence the enzyme
Covalent catalysis
Metal ion catalysis
Optimal temperature for

typical human enzyme
Rate of reaction
Eects of
Temperature
and pH
Optimal temperature for

enzyme of thermophilic
(heat-tolerant)
bacteria
40
0
60
20
80
Temperature (C)
(a) Optimal temperature for two enzymes
Each enzyme
has an op?mal
temperature in
which it can
func?on
Each enzyme
has an op?mal
pH in which it
can func?on
Optimal pH for pepsin

(stomach enzyme)
Rate of reaction
4
5
0
1
2
3
pH
(b) Optimal pH for two enzymes
Exergonic reac?ons
release energy to the
system.
G < 0
Exergonic reac?ons
proceed spontaneously
100
Optimal pH
for trypsin
(intestinal
enzyme)
Exergonic vs. Endergonic reac1ons
10
Endergonic reac?ons
absorb energy from the
system.
G > 0
Endergonic reac?ons
are not spontaneous
ATP powers cellular work by coupling

exergonic reac?ons to endergonic
reac?ons
A cell does three main kinds of work:
Chemical
Transport
Mechanical
To do work, cells manage energy resources by energy
coupling, the use of an exergonic process to drive an
endergonic one
Most energy coupling in cells is mediated by ATP
The Structure and Hydrolysis of ATP

ATP (adenosine triphosphate) is the cells energy shuPle
ATP is composed of ribose (a sugar), adenine (a
nitrogenous base), and three phosphate groups
Adenine
Phosphate groups
Ribose
ATP hydrolysis
The bonds between the phosphate groups of
ATP can be broken by hydrolysis
Energy is released from ATP when the terminal
phosphate bond is broken
This release of energy comes from the chemical
change to a state of lower free energy, not from
the phosphate bonds themselves
Adenosine triphosphate (ATP)
H 2O
Adenosine diphosphate (ADP)
How ATP Performs Work

The three types of cellular work (mechanical,
transport, and chemical) are powered by the
hydrolysis of ATP
In the cell, the energy from the exergonic
reac?on of ATP hydrolysis can be used to drive
an endergonic reac?on
Overall, the coupled reac?ons are exergonic
ATP drives endergonic reac?ons by

phosphoryla?on, transferring a phosphate
group to some other molecule, such as a
reactant
The recipient molecule is now phosphorylated
Membrane protein
NH2
Glu
Glutamic
acid
NH3
Glu
G = +3.4 kcal/mol
Glutamine
Ammonia
(a) Endergonic reaction

1 ATP phosphorylates
glutamic acid,
making the amino
acid less stable.
Glu
ATP
Enzyme A
P
Glu
Solute
+ ADP
P
Glu
NH3
Glu
Cytoskeletal track
+ Pi
(b) Coupled with ATP hydrolysis, an exergonic reaction
ATP
Motor protein
(c) Overall free-energy change
ADP
P
Vesicle
Enzyme B
Solute transported
(a) Transport work: ATP phosphorylates

transport proteins
ATP
NH2
2 Ammonia displaces
the phosphate group,
forming glutamine.
Pi
Protein moved
(b) Mechanical work: ATP binds noncovalently

to motor proteins, then is hydrolyzed
The Regenera?on of ATP

ATP is a renewable resource that is regenerated
by addi?on of a phosphate group to adenosine
diphosphate (ADP)
The energy to phosphorylate ADP comes from
catabolic reac?ons in the cell
The chemical poten?al energy temporarily
stored in ATP drives most cellular work
Free-energy change of reac1on

rG = rG + RT lnQr; Qr is the reac?on
quo?ent.
At equilibrium, rG = 0 and Qr = Keq so the
equa?on becomes rG = RT ln Keq; Keq is the
equilibium constant.
ATP + H2O
Energy from
catabolism (exergonic,
energy-releasing
processes)
ADP + P i
Energy for cellular

work (endergonic,
energy-consuming
processes)
Lecture #8: Enzyme regula3on

Reading: Chapter 6
Lecture outline: How enzymes are controlled
Enzyme cofactors
Enzyme inhibitors
Allosteric regula?on
Induced t model of enzyme catalysis
Overview
Cofactors help enzymes to func?on eciently
Enzyme inhibitors block ac?vity through
dierent mechanisms:
Compe??ve
Non-compe??ve
Uncompe??ve
Enzymes can be regulated by structural changes
Cofactors
Cofactors are nonprotein enzyme helpers
Cofactors may be inorganic (such as a metal in
ionic form) or organic
An organic cofactor is called a coenzyme
Coenzymes include vitamins
hGp://en.wikipedia.org/wiki/File:Induced_t_diagram.svg
Vitamin B12 is an example of a

coenzyme:
Cofactors
Tightly-bound cofactors are called prosthe3c
groups. Example: heme
Loosely-bound cofactors are called coenzymes.
An inac?ve enzyme lacking the cofactor is called
an apo-enzyme; the complete enzyme with its
cofactor is called a holoenzyme.
hGp://en.wikipedia.org/wiki/Vitamin_B12#Enzyme_func?on
Cofactors
Cofactors
Organic cofactors oYen share a common

chemical feature, can you see it?
NADH is reversibly oxidized to NAD+ during electron transport

in cells.
Many enzymes contain common structural features that bind NAD+/

NADH
Coenzyme A
NAD+
FAD
Rossmann fold in lactate dehydrogenase
Regula3on of enzyme ac3vity helps

control metabolism
Chemical chaos would result if a cells metabolic
pathways were not ?ghtly regulated
A cell does this by switching on or o the genes
that encode specic enzymes or by regula?ng
the ac?vity of enzymes
Active site
available
Isoleucine
used up by
cell
Initial substrate
(threonine)
Threonine
in active site
Enzyme 1
(threonine
deaminase)
Intermediate A
Active site of
Enzyme 2
enzyme 1 no
longer binds
threonine; Intermediate B
pathway is
switched off.
Enzyme 3
Feedback
inhibition
Isoleucine
binds to
Enzyme 1
and induces
structure
change
Intermediate C
Enzyme 4
Intermediate D
Enzyme 5
End product
(isoleucine)
Feedback Inhibi3on
In feedback inhibi3on, the end product of a
metabolic pathway shuts down the pathway
Feedback inhibi?on prevents a cell from was?ng
chemical resources by synthesizing more
product than is needed
Enzyme Inhibitors
Compe33ve inhibitors bind to the ac?ve site of
an enzyme, compe?ng with the substrate
Noncompe33ve inhibitors bind to another part
of an enzyme, causing the enzyme to change
shape and making the ac?ve site less eec?ve
Examples of inhibitors include toxins, poisons,
pes?cides, and an?bio?cs
Substrate
Active site
Competitive
inhibitor
Enzyme
Noncompetitive inhibitor
(a) Normal binding
(b) Competitive inhibition
Many an?bio?c drugs

bind and inhibit the bacterial
ribosome.

In this structure of the small ribosomal
subunit (30S) from Venki
Ramakrishnans lab, the
glowing molecule is the an?bio?c
binding near the decoding center.
(c) Noncompetitive inhibition
4 types of HIV-1 inhibitors

Video of chloramphenicol on 70S ribosome:

hGps://www.youtube.com/watch?v=dY-hP8Wd4sA
hGp://en.wikipedia.org/wiki/HAART
HIV protease inhibitors block the viral enzyme

required to produce individual HIV proteins
Allosteric Regula?on of Enzymes

Allosteric regula3on may either
inhibit or s?mulate an enzymes
ac?vity
Allosteric regula?on occurs
when a regulatory molecule
binds to a protein at one site
and aects the proteins
func?on at another site
ritonavir
Hemoglobin is a classic example of an allosterically regulated protein

hGp://en.wikipedia.org/wiki/Enzyme_inhibitor
Allosteric Ac3va3on and Inhibi3on

Most allosterically regulated enzymes are made
from polypep?de subunits
Each enzyme has ac?ve and inac?ve forms
The binding of an ac?vator stabilizes the ac?ve
form of the enzyme
The binding of an inhibitor stabilizes the inac?ve
form of the enzyme
Allosteric enyzme Active site

with four subunits (one of four)
Regulatory
site (one
of four)
Activator
Active form
Stabilized active form
Oscillation
NonInhibitor
functional Inactive form
active
site
Stabilized inactive
form
(a) Allosteric activators and inhibitors

Substrate
Inactive form
Stabilized active
form
(b) Cooperativity: another type of allosteric activation
Allosteric enzyme
with four subunits
Regulatory
site (one
of four)
Active site
(one of four)
Active form
The Hb tetramer includes two and two subunits
Activator
Stabilized active form
Oscillation
NonInhibitor
functional Inactive form
active
site
Stabilized inactive
form
Strong interac?ons between

the 1 and 1 (and 2 / 2)
subunits hold them together
even in the presence of urea
(a denaturant).

(a) Allosteric activators and inhibitors
Hb exists in 2 major conforma3ons
Movie: R-T state transi?on for Hb
hGp://biochem.web.utah.edu/iwasa/projects/hemoglobin.html
O2 will bind Hb in either state, but has much higher anity for Hb in the R state.

T state is stabilized by a greater number of ion pairs at the subunit interfaces. When
O2 binds, Hb conforma?on changes to the R state.
Coopera3vity is a form of allosteric regula?on

that can amplify enzyme ac?vity
In coopera?vity, binding by a substrate to one
ac?ve site stabilizes favorable conforma?onal
changes at all other subunits
Substrate
Inactive form
Stabilized active
form
(b) Cooperativity: another type of allosteric activation
Iden3ca3on of Allosteric Regulators
EXPERIMENT
Caspase 1
Allosteric regulators are aGrac?ve drug

candidates for enzyme regula?on
Inhibi?on of proteoly?c enzymes called
caspases may help management of
inappropriate inammatory responses
Active
site
Substrate
SH
Known active form
SH Allosteric
binding site
Allosteric
inhibitor
Known inactive form
SH
Active form can
bind substrate
SS
Hypothesis: allosteric
inhibitor locks enzyme
in inactive form

RESULTS
Caspase 1
Active form
Inhibitor
Allosterically
Inactive form
inhibited form
4. Explain how ATP performs cellular work

5. Explain why an investment of ac?va?on
energy is necessary to ini?ate a spontaneous
reac?on
6. Describe the mechanisms by which enzymes
lower ac?va?on energy
7. Describe how allosteric regulators may inhibit
or s?mulate the ac?vity of an enzyme
8. Explain how some enzyme inhibitors work
1. Dis?nguish between the following pairs of

terms: catabolic and anabolic pathways;
kine?c and poten?al energy; open and closed
systems; exergonic and endergonic reac?ons
2. In your own words, explain the second law of
thermodynamics and explain why it is not
violated by living organisms
3. Explain in general terms how cells obtain the
energy to do cellular work
Overview: Life Is Work
Lecture #9: Energe.cs
Living cells require energy from outside sources

Some animals, such as the giant panda, obtain
energy by ea6ng plants, and some animals feed
on other organisms that eat plants
Reading: Chapter 7
Lecture outline: Cellular respira6on
Redox reac6ons
Electron transport chain
Glycolysis
Light
energy
Energy ows into an

ecosystem as sunlight
and leaves as heat

Photosynthesis
generates O2 and
organic molecules,
which are used in
cellular respira6on

Cells use chemical
energy stored in
organic molecules to
regenerate ATP, which
powers work
ECOSYSTEM
Photosynthesis
in chloroplasts
CO2 + H2O
Cellular respira.on
in mitochondria
ATP
ATP powers most cellular work
Heat
energy
Organic
+ O
molecules 2
Video: How cells harvest energy

hLps://www.youtube.com/watch?v=-Gb2EzF_XqA
Catabolic Pathways and Produc.on of ATP

The breakdown of organic molecules is
exergonic
Fermenta.on is a par6al degrada6on of sugars
that occurs without O2
Aerobic respira.on consumes organic
molecules and O2 and yields ATP
Anaerobic respira.on is similar to aerobic
respira6on but consumes compounds other
than O2
Redox Reac.ons: Oxida.on and

Reduc.on
The transfer of electrons during chemical
reac6ons releases energy stored in organic
molecules
This released energy is ul6mately used to
synthesize ATP
The Principle of Redox

Chemical reac6ons that transfer electrons
between reactants are called oxida6on-reduc6on
reac6ons, or redox reac.ons
In oxida.on, a substance loses electrons, or is
oxidized
In reduc.on, a substance gains electrons, or is
reduced (the amount of posi6ve charge is
reduced)

becomes oxidized
(loses electron)
becomes reduced
(gains electron)
Reactants
The electron donor is called the reducing agent

The electron receptor is called the oxidizing
agent
Some redox reac6ons do not transfer electrons
but change the electron sharing in covalent
bonds
An example is the reac6on between methane
and O2
Oxida3on of Organic Fuel Molecules

During Cellular Respira3on
During cellular respira6on, the fuel (such as
glucose) is oxidized, and O2 is reduced:
becomes oxidized
becomes reduced
Products
becomes oxidized
becomes reduced
Methane
(reducing
agent)
Oxygen
(oxidizing
agent)
Carbon dioxide
Water
Stepwise Energy Harvest via NAD+ and

the Electron Transport Chain
In cellular respira.on, glucose and other organic molecules are broken
down in a series of steps
Electrons from organic compounds are usually rst transferred to NAD+,
a coenzyme
As an electron acceptor, NAD+ func6ons as an oxidizing agent during
cellular respira6on
Each NADH (the reduced form of NAD+) represents stored energy that is
tapped to synthesize ATP
R
R
Dehydrogenase
R
R
2 e + 2 H
+
+ H
2 e
+
NAD+
2[H]
H+
NADH
Dehydrogenase
Reduc.on of NAD+
Oxida.on of NADH
Nico.namide
(reduced
form)
Nico.namide
(oxidized
form)
Nico.namide Adenine Dinucleo.de
H2 + 1/2 O2
Controlled
release of
energy for
synthesis of
ATP
ATP
Free energy, G
ort
ransp
ron t ain
Elect
ch
Free energy, G
2 H+ + 2 e
Explosive
release of
heat and light
energy
1/ O
2 2
2 H
(from food via NADH)
ATP
2 e
H2O
1/ O
2 2
(a) Uncontrolled reac.on
H2O
(b) Cellular respira.on
NADH passes the electrons to the electron

transport chain
Unlike an uncontrolled reac6on, the electron
transport chain passes electrons in a series of
steps instead of one explosive reac6on
O2 pulls electrons down the chain in an energyyielding tumble
The energy yielded is used to regenerate ATP
The Stages of Cellular Respira6on: A

Preview
Cellular respira6on has three stages:
ATP
2 H+
H+
Glycolysis (breaks down glucose into two molecules

of pyruvate)
The citric acid cycle (completes the breakdown of
glucose)
Oxida.ve phosphoryla.on (accounts for most of
the ATP synthesis)
Electrons
carried
via NADH
Glycolysis
Citric
acid
cycle
Glycolysis
Pyruvate
Glucose
Electrons carried
via NADH and
FADH2
Electrons
carried
via NADH
Pyruvate
Glucose
Cytosol
Mitochondrion
Cytosol
ATP
ATP
ATP
Substrate-level
phosphoryla.on
Substrate-level
phosphoryla.on
Substrate-level
phosphoryla.on
Electrons carried
via NADH and
FADH2
Electrons
carried
via NADH
Citric
acid
cycle
Glycolysis
Pyruvate
Glucose
Oxida.ve
phosphoryla.on:
electron transport
and
chemiosmosis
Mitochondrion
Cytosol
ATP
ATP
ATP
Substrate-level
phosphoryla.on
Substrate-level
phosphoryla.on
Oxida.ve
phosphoryla.on
The process that generates most of the ATP is

called oxida.ve phosphoryla.on because it is
powered by redox reac6ons
Oxida6ve phosphoryla6on accounts for almost
90% of the ATP generated by cellular respira6on
A smaller amount of ATP is formed in glycolysis
and the citric acid cycle by substrate-level
phosphoryla.on
Glycolysis harvests chemical energy by

oxidizing glucose to pyruvate
Enzyme
Enzyme
ADP
P
Substrate
ATP
Glycolysis (splibng of sugar) breaks down

glucose into two molecules of pyruvate
Glycolysis occurs in the cytoplasm and has two
major phases:
Energy investment phase
Energy payo phase
Product
Energy investment phase

Glucose
Glucose
ATP
1
Hexokinase
ADP
2 ADP + 2
2 ATP
used
Glucose
Glucose-6-phosphate
Energy payo phase

4 ADP + 4
ATP
P
2 NAD+ + 4 e + 4 H+
4 ATP
2 NADH
Glucose
4 ATP formed 2 ATP used

2 NAD+ + 4 e + 4 H+
ADP
+ 2 H+
2 Pyruvate + 2 H2O
Net
1
Hexokinase
formed
Phosphoryla6on makes sugar more

reac6ve; charge traps sugar in cell
2 Pyruvate + 2 H2O
2 ATP
2 NADH + 2 H+
Glucose-6-phosphate
Fig. 9-9-3
Glucose
Glucose
ATP
ATP
1
Hexokinase
1
Hexokinase
ADP
ADP
Fructose-6-phosphate
Glucose-6-phosphate
2
Phosphoglucoisomerase
Glucose-6-phosphate
Glucose-6-phosphate
2
2
Phosphogluco-
isomerase
ATP
3
Phosphofructo-
kinase
ATP
ADP
3
Phosphofructokinase
ADP
Fructose-
1, 6-bisphosphate
Fructose-
1, 6-bisphosphate
Key step in regula6ng glycolysis
2 NAD+
2 NADH
+ 2 H+
6
Triose phosphate
dehydrogenase
2 Pi
Glucose
ATP
1
Hexokinase
2 1, 3-Bisphosphoglycerate
ADP
2
Glucose-6-phosphate
2
ATP
2 NAD+
Fructose-
1, 6-bisphosphate
4
Aldolase
3
Phosphofructokinase
2 NADH
Glyceraldehyde-
3-phosphate
6
Triose phosphate
dehydrogenase
2Pi
+ 2 H+
ADP
Isomerase
Fructose-
1, 6-bisphosphate
4
Aldolase
5
Isomerase
Dihydroxyacetone
phosphate
Glyceraldehyde-
3-phosphate
Dihydroxyacetone
phosphate
Glyceraldehyde-
3-phosphate
Glyceraldehyde phosphate dehydrogenase (GAPDH)
2 NAD+
2 NADH
+ 2 H+
2 NAD+
6
Triose phosphate
dehydrogenase
Triose phosphate
dehydrogenase
2 Pi
2P
2 NADH
+ 2 H+
2 ADP
2 ADP
7 Phosphoglycerokinase
Phosphoglycerokinase
2 ATP
2 ATP
2 ADP
2
3-Phosphoglycerate
2 ATP
7
Phosphoglycero-
kinase
3-Phosphoglycerate
2 NAD+
3-Phosphoglycerate
2-Phosphoglycerate
2 NAD+
8
Phosphoglycero-
mutase
2-Phosphoglycerate
6
Triose phosphate
dehydrogenase
Triose phosphate
dehydrogenase
2 Pi
2 NADH
+ 2 H+
3-Phosphoglycerate
Phosphoglyceromutase
2 Pi
2 NADH
+ 2 H+
2 ADP
2 ADP
2 ATP
2 ATP
2
2
3-Phosphoglycerate
2-Phosphoglycerate
3-Phosphoglycerate
2 H2O
2-Phosphoglycerate
Enolase
2 ATP
2
2-Phosphoglycerate
9
2 H2O
10
Pyruvate kinase
8
Phosphoenolpyruvate
2 ADP
Enolase
2 H2O
Enolase
2 Phosphoenolpyruvate
2 ADP
Phosphoenolpyruvate
2 ATP
10
Pyruvate kinase
Phosphoenolpyruvate
2
Pyruvate
Pyruvate
Warburg eect
Tumor cells have glycoly6c rates up to 200X
higher than those of normal cells in their
6ssue of origin.
Can be used to diagnose tumors, using an 18Flabeled substrate of hexokinase and PET
scanning.
Reasons: low-oxygen environment of tumors,
tumor-associated pyruvate kinase enzyme,
damage or shutdown of mitochondria
Lecture #10: Aerobic metabolism

Reading: Chapter 7
In the presence of O2, pyruvate enters the

mitochondrion
Before the citric acid cycle can begin, pyruvate
must be converted to acetyl CoA, which links
the cycle to glycolysis

Lecture outline:
Citric acid cycle
Oxida8ve phosphoryla8on
CYTOSOL
MITOCHONDRION
NAD+
NADH
+ H+
1
Pyruvate
Transport protein
3
CO2
The citric acid cycle completes the energyyielding oxida=on of organic molecules
Coenzyme A
Acetyl CoA
Mitochondria: Chemical Energy

Conversion
Mitochondria are in nearly all eukaryo8c cells
They have a smooth outer membrane and an
inner membrane folded into cristae
The inner membrane creates two
compartments: intermembrane space and
mitochondrial matrix
Some metabolic steps of cellular respira8on are
catalyzed in the mitochondrial matrix
Cristae present a large surface area for enzymes
that synthesize ATP
Intermembrane space
Outer
membrane
The citric acid cycle, also called the Krebs cycle

or the tricarboxylic acid (TCA) cycle, takes place
within the mitochondrial matrix
The cycle oxidizes organic fuel derived from
pyruvate, genera8ng 1 ATP, 3 NADH, and 1
FADH2 per turn
Free ribosomes
in the
mitochondrial
matrix
Inner
membrane
Cristae
Matrix
0.1 m
Remember:
NADH = reduced form of Nico8namide
Adenine Dinucleo8de
New, but related molecule:
FADH2 = Flavin Adenine Dinucleo8de

Pyruvate
CO2
NAD+
CoA
NADH
+ H+
Acetyl CoA
CoA
CoA
hUp://vcell.ndsu.nodak.edu/anima8ons/citricacid_overview/movie-ash.htm
Citric
acid
cycle
FADH2
2 CO2
3 NAD+
3 NADH
FAD
+ 3 H+
ADP + P i
ATP
Acetyl CoA
The citric acid cycle has eight steps, each

catalyzed by a specic enzyme
The acetyl group of acetyl CoA joins the cycle by
combining with oxaloacetate, forming citrate
The next seven steps decompose the citrate
back to oxaloacetate, making the process a
cycle
CoASH
Oxaloacetate
Citrate
Citric
acid
cycle
The NADH and FADH2 produced by the cycle

relay electrons extracted from food to the
electron transport chain

Acetyl CoA
Acetyl CoA
CoASH
CoASH
Oxaloacetate
H2O
Oxaloacetate
Citrate
Citric
acid
cycle
H2O
Citrate
Isocitrate
Isocitrate
NAD+
Citric
acid
cycle
NADH
+ H+
CO2
-Keto-
glutarate
Acetyl CoA
Acetyl CoA
CoASH
CoASH
H2O
Oxaloacetate
H2O
Oxaloacetate
Citrate
Citrate
Isocitrate
Isocitrate
NAD+
Citric
acid
cycle
NAD+
Citric
acid
cycle
NADH
+ H+
CO2
NADH
+ H+
CO2
CoASH
CoASH
-Keto-
glutarate
CO2
NAD+
CO2
NAD+
Succinate
NADH
+ H+
Succinyl
CoA
-Keto-
glutarate
CoASH
Pi
GTP GDP
NADH
+ H+
Succinyl
CoA
ADP
ATP
Acetyl CoA
Acetyl CoA
CoASH
CoASH
H2O
Oxaloacetate
H2O
Oxaloacetate
Malate
Citrate
Citrate
Isocitrate
Isocitrate
NAD+
Citric
acid
cycle
Fumarate
NAD+
NADH
+ H+
CO2
H2O
Fumarate
CoASH
-Keto-
glutarate
CoASH
FADH2
NAD+
FAD
Succinate
Pi
GTP GDP
ADP
Succinyl
CoA
Citric
acid
cycle
NADH
+ H+
CO2
CO2
CoASH
-Keto-
glutarate
CoASH
FADH2
NAD+
FAD
Succinate
Pi
GTP GDP
ADP
ATP
NADH
+ H+
ATP
Succinyl
CoA
NADH
+ H+
CO2
During oxida=ve phosphoryla=on, chemiosmosis

couples electron transport to ATP synthesis
Acetyl CoA
CoASH
NADH
+H+
H2O
NAD+
8
Oxaloacetate
Malate
Citrate
Isocitrate
NAD+
H2O
Citric
acid
cycle
Fumarate
NADH
+ H+
CO2
CoASH
-Keto-
glutarate
CoASH
FADH2
NAD+
FAD
Succinate
Pi
GTP GDP
Succinyl
CoA
Following glycolysis and the citric acid cycle,

NADH and FADH2 account for most of the
energy extracted from food
These two electron carriers donate electrons to
the electron transport chain, which powers ATP
synthesis via oxida8ve phosphoryla8on
CO2
NADH
+ H+
ADP
ATP
The Pathway of Electron Transport
NADH
50
NAD+
FADH2
2 e
40
FMN
FAD
FAD
FeS
FeS
Free energy (G) rela=ve to O2 (kcal/mol)
The electron transport chain is in the cristae of

the mitochondrion
Most of the chains components are proteins,
which exist in mul8protein complexes
The carriers alternate reduced and oxidized
states as they accept and donate electrons
Electrons drop in free energy as they go down
the chain and are nally passed to O2, forming
H2O
2 e
Cyt b
30
Mul=protein
complexes
FeS
Cyt c1
IV
Cyt c
Cyt a
Cyt a3
20
10
2 e
(from NADH
or FADH2)
2 H+ + 1/2
O2
H2O
Chemiosmosis: The Energy-Coupling

Mechanism
Electrons are transferred from NADH or FADH2
to the electron transport chain
Electrons are passed through a number of
proteins including cytochromes (each with an
iron atom) to O2
The electron transport chain generates no ATP
The chains func8on is to break the large freeenergy drop from food to O2 into smaller steps
that release energy in manageable amounts
Electron transfer in the electron transport chain

causes proteins to pump H+ from the mitochondrial
matrix to the intermembrane space
H+ then moves back across the membrane, passing
through channels in ATP synthase
ATP synthase uses the exergonic ow of H+ to drive
phosphoryla8on of ATP
This is an example of chemiosmosis, the use of
energy in a H+ gradient to drive cellular work
INTERMEMBRANE SPACE
H+
Stator
Rotor
Internal
rod
Cata-
ly=c
knob
ADP
+
P
ATP
MITOCHONDRIAL MATRIX
ATP Synthase: A Nanomachine

1 - H+ ions (protons) enter channel in stator

2- Protons bind specic sites in the rotor, causing
conforma8onal changes that act to spin the rotor
within the membrane

3- Each proton makes 1 complete turn before entering
the mitochondrial matrix through another channel in
the stator

4- rotor spinning causes the internal rod to spin. The rod
extends into the sta8onary cataly8c knob

5- turning of the rod ac8vates cataly8c sites in the knob
that produce ATP from ADP and Pi
hUp://www.youtube.com/watch?v=PjdPTY1wHdQ
The energy stored in a H+ gradient across a

membrane couples the redox reac8ons of the
electron transport chain to ATP synthesis
The H+ gradient is referred to as a protonmo=ve force, emphasizing its capacity to do
work
H+
H+
H+
Protein complex
of electron
carriers
H+
Cyt c
FADH2
FAD
ATP
synthase
H2O
2 H+ + 1/2O2
NAD+
NADH
ADP + P i
(carrying electrons
from food)
ATP
H+
2 Chemiosmosis
1 Electron transport chain
Oxida=ve phosphoryla=on
An Accoun8ng of ATP Produc8on by

Cellular Respira8on
During cellular respira8on, most energy ows in
this sequence:
glucose NADH electron transport chain
proton-mo8ve force ATP
About 40% of the energy in a glucose molecule
is transferred to ATP during cellular respira8on,
making about 38 ATP molecules
Overall respira8on eciency is ~35%, meaning that 35% of energy stored in glucose is harvested
Electron shueles
span membrane
CYTOSOL
MITOCHONDRION
2 NADH
or
2 FADH2
2 NADH
Glycolysis
2
Pyruvate
Glucose
6 NADH
2 NADH
2
Acetyl
CoA
+ 2 ATP
Maximum per glucose:
2 FADH2
Citric
acid
cycle
Oxida=ve
phosphoryla=on:
electron transport
and
chemiosmosis
+ 2 ATP
+ about 32 or 34 ATP
26-28 ATP
About
36-38 ATP
30-32 ATP
3 reasons for inexact ATP yield es8mate: - phosphoryla8on and redox rxns not directly coupled,

so NADH:ATP not a whole number

- ATP yield varies depending on electron transport sys

- PMF used to drive other kinds of work
How do bacteria do it???
They lack membrane-bound organelles (i.e. mitochondrion)

but have two cellular membranes!
Lecture #11: Anaerobic metabolism

Reading: Chapter 7
Fermenta5on and anaerobic

respira5on enable cells to produce ATP without
using oxygen
Most cellular respira7on requires O2 to produce
ATP
Glycolysis can produce ATP with or without O2
(in aerobic or anaerobic condi7ons)
In the absence of O2, glycolysis couples with
fermenta7on or anaerobic respira7on to
produce ATP
Lecture outline:
Fermenta7on
Anaerobic respira7on
Regula7on of cellular respira7on
How do Prokaryotes do it???

Anaerobic respira7on uses an electron transport
chain with an electron acceptor other than O2, for
example sulfate (SO42-)
Fermenta7on uses substrate-level phosphoryla7on
instead of an electron transport chain to generate
ATP
Enzyme
Enzyme
ADP
Substrate
ATP
Product
They lack membrane-bound organelles (i.e. mitochondrion)

but have two cellular membranes!
Types of Fermenta7on
Sulfate-reducing bacteria
Fermenta7on consists of glycolysis plus

reac7ons that regenerate NAD+, which can be
reused by glycolysis
Two common types are alcohol fermenta7on
and lac7c acid fermenta7on
2 NAD+
2 NADH
+ 2 H+
2 ADP + 2 P
In alcohol fermenta5on, pyruvate is converted

to ethanol in two steps, with the rst releasing
CO2
Alcohol fermenta7on by yeast is used in
brewing, winemaking, and baking
Glucose
Ethanol
Lac5c Acid
2 ATP
Glycolysis
2 Pyruvate
2 NAD+
2 Ethanol
(a) Alcohol fermenta5on
2 NADH
+ 2 H+
2 CO2
2 Acetaldehyde
Anaerobic fermenta5on
In lac5c acid fermenta5on, pyruvate is reduced
by NADH, forming lactate as an end product,
with no release of CO2
Lac7c acid fermenta7on by some fungi and
bacteria is used to make cheese and yogurt
Human muscle cells use lac7c acid fermenta7on
to generate ATP when O2 is scarce
2 ADP + 2
Glucose
2 Lactate
(b) Lac5c acid fermenta5on
2 NADH
+ 2 H+
C6H12O6 + 2 ADP + 2 phosphate 2 lac7c acid + 2 ATP
The energy released in this equa7on is

approximately 150 kJ per mole, which is
harvested in genera7ng 2 ATP from ADP.
This is only 5% of the energy per sugar
molecule that the typical aerobic reac7on
generates.
Comparing Fermenta7on to Aerobic and

Anaerobic Respira7on
2 ATP
Glycolysis
2 NAD+
Fermenta7ve anaerobic organisms mostly use

the lac7c acid fermenta7on pathway
2 Pyruvate
All 3 processes use glycolysis to oxidize glucose and

other organic fuels to pyruvate
In all 3 pathways, NAD+ is oxidizing agent that
accepts electrons from food during glycolysis
The processes have dierent nal electron
acceptors: an organic molecule (such as pyruvate
or acetaldehyde) in fermenta7on, O2 in aerobic
respira7on and another molecule, i.e. SO42-, in
anaerobic respira7on
Respira7on produces 38 32-34 ATP per glucose
molecule; fermenta7on produces 2 ATP per
glucose molecule
Glucose
Obligate anaerobes carry out fermenta7on or

anaerobic respira7on and cannot survive in the
presence of O2
Yeast and many bacteria are faculta5ve
anaerobes, meaning that they can survive using
either fermenta7on or cellular respira7on
In a faculta7ve anaerobe, pyruvate is a fork in
the metabolic road that leads to two alterna7ve
catabolic routes
The Evolu5onary Signicance of

Glycolysis
Glycolysis occurs in nearly all organisms
Glycolysis probably evolved in ancient
prokaryotes before there was oxygen in the
atmosphere
CYTOSOL
Glycolysis
Pyruvate
No O2 present:
Fermenta5on
O2 present:
Aerobic cellular
respira5on
MITOCHONDRION
Ethanol
or
lactate
Acetyl CoA
Citric
acid
cycle
Glycolysis and the citric acid cycle connect

to many other metabolic pathways
Glycolysis and the citric
acid cycle are major
intersec7ons to various
catabolic and anabolic
pathways
The Versa5lity of Catabolism

Catabolic pathways funnel electrons from many
kinds of organic molecules into cellular
respira7on
Glycolysis accepts a wide range of
carbohydrates
Proteins must be digested to amino acids;
amino acids can feed glycolysis or the citric acid
cycle
Fats are digested to glycerol (used in glycolysis)

and faby acids (used in genera7ng acetyl CoA)
Faby acids are broken down by beta oxida5on
and yield acetyl CoA
An oxidized gram of fat produces more than
twice as much ATP as an oxidized gram of
carbohydrate
Proteins
Carbohydrates
Amino
acids
Sugars
Fats
Glycerol
Glycolysis
Glucose
Glyceraldehyde-3-
hbps://www.youtube.com/watch?v=J5wGPHm-2og
NH3
Pyruvate
Acetyl CoA
Citric
acid
cycle
Oxida5ve
phosphoryla5on
FaZy
acids
Biosynthesis (Anabolic Pathways)

The body uses small molecules to build other substances
These small molecules may come directly from food, from
glycolysis, or from the citric acid cycle
Regula7on of Cellular Respira7on via

Feedback Mechanisms
Feedback inhibi7on is the most common
mechanism for control
If ATP concentra7on begins to drop, respira7on
speeds up; when there is plenty of ATP,
respira7on slows down
Control of catabolism is based mainly on
regula7ng the ac7vity of enzymes at strategic
points in the catabolic pathway
Glucose
Glycolysis
Inhibits
AMP
S5mulates
+
Glucose
ATP
1
Hexokinase
Phosphofructokinase
Fructose-1,6-bisphosphate
ADP
Inhibits
Glucose-6-phosphate
2
Pyruvate
ATP
ADP
Phosphofructo-
kinase
ATP
ATP
Acetyl CoA
Citric
acid
cycle
Oxida5ve
phosphoryla5on
3
Phosphofructokinase
Citrate
ADP
Fructose-
1, 6-bisphosphate
Fructose-
1, 6-bisphosphate
ATP is a natural allosteric inhibitor of PFK, in order to prevent unnecessary

produc7on of ATP through glycolysis.
Phosphofructokinase
hbps://www.youtube.com/watch?v=rb4jImee4NU
There is a concerted transi7on from an enzyma7cally inac7ve T-state to the ac7ve R-state.
F6P binds with a high anity to the R state but not the T state enzyme. For every molecule of
F6P that binds to PFK1, the enzyme progressively shiis from T state to the R state.
Electron shuttles
span membrane
2 NADH
Glycolysis
2 Pyruvate
Glucose
H+
2 NADH
Pyruvate oxidation
2 Acetyl CoA
6 NADH
Citric
acid
cycle
+ 2 ATP
+ 2 ATP
Maximum per glucose:

CYTOSOL
MITOCHONDRION
2 NADH
or
2 FADH2
INTER-
MEMBRANE
SPACE
About
30 or 32 ATP
2 FADH2
Oxidative
phosphorylation:
electron transport
and
chemiosmosis
ATP
synthase
+ about 26 or 28 ATP
ADP +
MITO-
CHONDRIAL
MATRIX
ATP
i
H+
Chemiosmosis
Fermenta5on and Aerobic Respira5on

Compared
Both processes use glycolysis to oxidize glucose
and other organic fuels to pyruvate
The processes have dierent nal electron
acceptors: an organic molecule (such as
pyruvate or acetaldehyde) in fermenta7on and
O2 in cellular respira7on
Cellular respira7on produces 32 ATP per glucose
molecule; fermenta7on produces 2 ATP per
glucose molecule
hbp://en.wikipedia.org/wiki/Chemiosmosis
Two examples of uncoupling between

glycolysis and aerobic metabolism
Hiberna7on
Warburg eect
Hiberna5on
Animals that hibernate have large numbers of
brown fat cells packed full of mitochondria
These cells can express a mitochondrial
uncoupler in the inner mito membrane that
allows H+ ions to ow back into the matrix
Uncouplers enable ongoing oxida7on of
stored fuels (fats) without genera7ng ATP and
instead producing heat

1. Explain in general terms how redox reac7ons
are involved in energy exchanges
2. Name the three stages of cellular respira7on;
for each, state the region of the eukaryo7c cell
where it occurs and the products that result
3. In general terms, explain the role of the
electron transport chain in cellular respira7on
4. Explain where and how the respiratory

electron transport chain creates a proton
gradient
5. Dis7nguish between fermenta7on and
anaerobic respira7on
6. Dis7nguish between obligate and faculta7ve
anaerobes
Lecture #12: Photosynthesis I

Reading: Chapter 8
Lecture outline: Intro to Photosynthesis
Light energy to chemical energy
Light reac:ons
Autotrophs sustain themselves without ea:ng

anything derived from other organisms
Autotrophs are the producers of the biosphere,
producing organic molecules from CO2 and
other inorganic molecules
Almost all plants are photoautotrophs, using the
energy of sunlight to make organic molecules
from H2O and CO2
Overview: The Process That Feeds the

Biosphere
Photosynthesis is the process that converts
solar energy into chemical energy
Directly or indirectly, photosynthesis nourishes
the living world
Photosynthesis occurs
in plants, algae, certain
other pro:sts, and
some prokaryotes
These organisms feed
not only themselves but
also most of the living
world
(a) Plants
(c) Unicellular proBst
10 m
(e) Purple sulfur

bacteria
(b) MulBcellular alga
(d) Cyanobacteria
40 m
1.5 m
Heterotrophs obtain their organic material from

other organisms
Heterotrophs are the consumers of the
biosphere
Almost all heterotrophs, including humans,
depend on photoautotrophs for food and O2
Photosynthesis converts light energy to

the chemical energy of food
Chloroplasts are structurally similar to and likely
evolved from photosynthe:c bacteria
The structural organiza:on of photosynthe:c
cells allows for the chemical reac:ons of
photosynthesis

Chloroplasts: The Sites of Photosynthesis in

Plants
Leaves are the major loca:ons of
photosynthesis
Their green color is from chlorophyll, the green
pigment within chloroplasts
Light energy absorbed by chlorophyll drives the
synthesis of organic molecules in the chloroplast
CO2 enters and O2 exits the leaf through
microscopic pores called stomata
Leaf cross secBon

Vein
Mesophyll
Chloroplasts are found

mainly in cells of the
mesophyll, the interior
:ssue of the leaf
A typical mesophyll cell
has 3040 chloroplasts
The chlorophyll is in the
membranes of
thylakoids (connected
sacs in the chloroplast);
thylakoids may be
stacked in columns called
grana
Chloroplasts also contain
stroma, a dense uid
Stomata
Chloroplast
CO2
O2
Mesophyll cell
Outer
membrane
Stroma

Thylakoid

Granum

Thylakoid
space
Intermembrane
space
Inner
membrane
1 m
5 m
Tracking Atoms Through

Photosynthesis:
Photosynthesis can be summarized as the following equa:on:
Photosynthesis as a Redox Process

Photosynthesis is a redox process in which H2O
is oxidized and CO2 is reduced
6 CO2 + 12 H2O + Light energy C6H12O6 + 6 O2 + 6 H2O
Chloroplasts split H2O into hydrogen and oxygen,

incorpora:ng the electrons of hydrogen into sugar molecules
Reactants:
Products:
6 CO2
C6H12O6
Energy + 6CO2 + 6H2O
12 H2O
6 H2O
6 O2
C6H12O6 + 6O2
Endergonic reac:on!
The Two Stages of Photosynthesis: A

Preview
Photosynthesis consists of the light reacBons
(the photo part) and Calvin cycle (the synthesis
part)
The light reac:ons (in the thylakoids):
Split H2O
Release O2
Reduce NADP+ to NADPH
Generate ATP from ADP by photophosphorylaBon
The Calvin cycle (in the stroma) forms sugar

from CO2, using ATP and NADPH
The Calvin cycle begins with carbon xaBon,
incorpora:ng CO2 into organic molecules
NADP+
H2O
Light
NADP+
ADP
+ P i
Light
ReacBons
h[ps://www.youtube.com/watch?v=YeD9idmcX0w
Chloroplast
H2O
CO2
H2O
Light
Light
NADP+
NADP+
ADP
ADP
+ P i
+ P i
Light
ReacBons
Chloroplast
Light
ReacBons
ATP
ATP
NADPH
NADPH
Chloroplast
O2
O2
Calvin
Cycle
CO2
H2O
Light
NADP+
ADP
+ P i
Light
ReacBons
Calvin
Cycle
ATP
The light reac:ons convert solar energy

to the chemical energy of ATP and
NADPH
Chloroplasts are solar-powered chemical
factories
Their thylakoids transform light energy into the
chemical energy of ATP and NADPH
NADPH
Chloroplast
O2
[CH2O]
(sugar)
The Nature of Sunlight

Light is a form of electromagne:c energy, also
called electromagne:c radia:on
Like other electromagne:c energy, light travels
in rhythmic waves
Wavelength is the distance between crests of
waves
Wavelength determines the type of
electromagne:c energy
The electromagneBc spectrum is the en:re

range of electromagne:c energy, or radia:on
Visible light consists of wavelengths (including
those that drive photosynthesis) that produce
colors we can see (380-750 nm)
Light also behaves as though it consists of
discrete par:cles, called photons
105 nm
103 nm
103 nm
1 nm
Gamma
X-rays
rays
UV
106 nm
Infrared
1 m
(109 nm)
Micro-
waves
103 m
Radio
waves
Visible light
380
450
500
550
600
650
700
750 nm
Photosynthe:c Pigments: The Light

Receptors
Pigments are substances that absorb visible
light
Dierent pigments absorb dierent
wavelengths
Wavelengths that are not absorbed are
reected or transmi[ed
Leaves appear green because chlorophyll
reects and transmits green light
Longer wavelength
Lower energy
Shorter wavelength
Higher energy
Light
Reected
light
Chloroplast
Absorbed
light
Granum
Transmieed
light
A spectrophotometer measures a pigments

ability to absorb various wavelengths
This machine sends light through pigments and
measures the frac:on of light transmi[ed at
each wavelength
TECHNIQUE
Chlorophyll Photoelectric
soluBon
tube
Galvanometer
Slit moves to
pass light
of selected
wavelength
The high transmieance

(low absorpBon)
reading indicates that
chlorophyll absorbs
very liele green light.

An absorpBon spectrum is a graph ploing a

pigments light absorp:on versus wavelength
The absorp:on spectrum of chlorophyll a
suggests that violet-blue and red light work best
for photosynthesis
An acBon spectrum proles the rela:ve
eec:veness of dierent wavelengths of
radia:on in driving a process
The low transmieance

(high absorpBon)
reading indicates that
chlorophyll absorbs
most blue light.

3 types of pigments in chloroplasts: chlorophyll a par:cipates directly in the light reac:ons

chlorophyll b is an accessory pigment

carotenoids are accessory pigments
Green
light
Blue
light
RESULTS
The ac:on spectrum of photosynthesis was rst

demonstrated in 1883 by Theodor W.
Engelmann
In his experiment, he exposed dierent
segments of a lamentous alga to dierent
wavelengths
Areas receiving wavelengths favorable to
photosynthesis produced excess O2
He used the growth of aerobic bacteria
clustered along the alga as a measure of O2
produc:on
AbsorpBon of light by
chloroplast pigments
Chloro-
phyll a
Carotenoids
400
(a) AbsorpBon spectra
Chlorophyll b
500
600
700
Wavelength of light (nm)
(b) AcBon spectrum
Rate of photosynthesis
(measured by O2 release)
RefracBng
prism
White
light
Aerobic bacteria
Filament
of alga
(c) Engelmanns
experiment
400
500
600
700
CH3
CHO
in chlorophyll a
in chlorophyll b
Porphyrin ring:
light-absorbing
head of molecule;
note magnesium
atom at center
Chlorophyll a is the main photosynthe:c

pigment
Accessory pigments, such as chlorophyll b,
broaden the spectrum used for photosynthesis
Accessory pigments called carotenoids absorb
excessive light that would damage chlorophyll
Hydrocarbon tail:
interacts with hydrophobic
regions of proteins inside
thylakoid membranes of
chloroplasts; H atoms not
shown

Excita:on of Chlorophyll by Light

e
Energy of electron
When a pigment absorbs light, it goes from a

ground state to an excited state, which is
unstable
When excited electrons fall back to the ground
state, photons are given o, an akerglow called
uorescence
If illuminated, an isolated solu:on of chlorophyll
will uoresce, giving o light and heat
Excited
state
Heat
Photon
(uorescence)
Photon
Chlorophyll
molecule
Ground
state
(a) ExcitaBon of isolated chlorophyll molecule
(b) Fluorescence
Lecture #13: Photosynthesis II

Reading: Chapter 8
Lecture outline: Carbon xa8on
Photosystems
The Calvin cycle
C4 and CAM plants
Energy of electron
Excited
state
Heat
Photon
(uorescence)
Photon
Chlorophyll
molecule
Ground
state
(a) Excita9on of isolated chlorophyll molecule
A Photosystem: A Reac8on-Center
Complex Associated with LightHarves8ng Complexes
A photosystem consists of a reac9on-center
complex (a type of protein complex)
surrounded by light-harves8ng complexes
The light-harves9ng complexes (pigment
molecules bound to proteins) funnel the energy
of photons to the reac8on center

(b) Fluorescence
A primary electron acceptor in the reac8on

center accepts an excited electron from
chlorophyll a
Solar-powered transfer of an electron from a
chlorophyll a molecule to the primary electron
acceptor is the rst step of the light reac8ons
Crystal structure of PS II
20 proteins
35 chlorophyll a molecules
12 carotenoids
25 integral lipids

Plastoquinones bind in specic sites
QB is a plastoquinone; isoprenoid tail extends

toward the thylakoid membrane.
Guskov et al (2009) NSMB
Photosystem
Photon
Thylakoid membrane
Light-harves9ng
complexes
Reac9on-center
complex
STROMA
Primary
electron
acceptor
hWp://vcell.ndsu.nodak.edu/anima8ons/
photosystemII/movie-ash.htm
Transfer
of energy
Guskov et al (2009) NSMB
Special pair of
chlorophyll a
molecules
Pigment
molecules
THYLAKOID SPACE
(INTERIOR OF THYLAKOID)
There are two types of photosystems in the

thylakoid membrane
Photosystem II (PS II) func8ons rst (the numbers
reect order of discovery) and is best at absorbing
a wavelength of 680 nm
The reac8on-center chlorophyll a of PS II is called
P680

Photosystem I (PS I) is best at absorbing a

wavelength of 700 nm
The reac8on-center chlorophyll a of PS I is
called P700
Linear Electron Flow

During the light reac8ons, there are two
possible routes for electron ow: cyclic and
linear
Linear electron ow, the primary pathway,
involves both photosystems and produces ATP
and NADPH using light energy
A photon hits a pigment

and its energy is passed
among pigment molecules
un8l it excites P680
An excited electron from
P680 is transferred to the
primary electron acceptor
Primary
acceptor
e
P680
1 Light
Pigment
molecules
Photosystem II
(PS II)
P680+ (P680 that is missing

an electron) is a very strong
oxidizing agent
H2O is split by enzymes, and
the electrons are transferred
from the hydrogen atoms to
P680+, thus reducing it to
P680
H+ are released in to the
thylakoid lumen
O2 is released as a byproduct of this reac8on
Primary
acceptor
2 H+
+
1/ O
2
2
H2O
3
e
e
P680
1 Light
Pigment
molecules
Photosystem II
(PS II)
H2O
H2O
Pq
Cytochrome
complex
Pc
e
e
5
P680
1 Light
ATP
Each electron falls

down an electron
transport chain from the
primary electron acceptor
of PS II to PS I
Energy released by the
fall drives the crea8on of
a proton gradient across
the thylakoid membrane
Diusion of H+ (protons)
across the membrane
drives ATP synthesis
Pigment
molecules
Primary
acceptor
Pq
Cytochrome
complex
Pc
e
e
P700
5
P680
Light
1 Light
6
ATP
Pigment
molecules
Photosystem II
(PS II)
2 H+
+
1/ O
2
2
Photosystem II
(PS II)
Primary
acceptor
2 H+
+
1/ O
2
2
Primary
acceptor
Photosystem I
(PS I)
In PS I (like PS II), transferred light energy excites P700, which

loses an electron to an electron acceptor
P700+ (P700 that is missing an electron) accepts an electron
passed down from PS II via the electron transport chain
Each electron falls down an electron transport

chain from the primary electron acceptor of PS I
to the protein ferredoxin (Fd) no proton
gradient created and hence no ATP generated
The electrons are then transferred to NADP+
and reduce it to NADPH
The electrons of NADPH are available for the
reac8ons of the Calvin cycle
Primary
acceptor
2 H+
+
1/ O
2
2
H2O
Primary
acceptor
Pq
Cytochrome
complex
Cyclic electron ow uses only photosystem I and

produces ATP, but not NADPH
Cyclic electron ow generates surplus ATP, sa8sfying the
higher demand in the Calvin cycle
Fd
e
e
8
NADP+
reductase
Pc
e
e
NADP+
+ H+

NADPH

P700
5
P680
Primary
acceptor
Light
1 Light
Primary
acceptor
Fd
Fd
Pq
NADP+
reductase
Cytochrome
complex
ATP
Pigment
molecules
Photosystem II
(PS II)
NADP+
+ H+
NADPH
Pc
Photosystem I
(PS I)
Photosystem I
Photosystem II
ATP
A Comparison of Chemiosmosis in
Chloroplasts and Mitochondria
Chloroplasts and mitochondria generate ATP by
chemiosmosis, but use dierent sources of
energy
Mitochondria transfer chemical energy from
food to ATP; chloroplasts transform light energy
into the chemical energy of ATP
Spa8al organiza8on of chemiosmosis diers
between chloroplasts and mitochondria but also
shows similari8es
In mitochondria, protons are pumped to the

intermembrane space and drive ATP synthesis
as they diuse back into the mitochondrial
matrix
In chloroplasts, protons are pumped into the
thylakoid space and drive ATP synthesis as they
diuse back into the stroma
Mitochondrion
Chloroplast
STROMA
(low H+ concentra9on)
Cytochrome
complex
Photosystem II
4 H+
Light
Photosystem I
Light
Fd
NADP+
reductase
H2O
MITOCHONDRION
STRUCTURE
CHLOROPLAST
STRUCTURE
H+
Intermembrane
space
Inner
membrane
Diusion
Electron
transport
chain
Key
Higher [H+]
Lower [H+]
+2 H+
Stroma
H+
ATP
The Calvin cycle uses ATP and NADPH to

convert CO2 to sugar
The Calvin cycle, like the citric acid cycle,
regenerates its star8ng material aher molecules
enter and leave the cycle
The cycle builds sugar from smaller molecules
by using ATP and the reducing power of
electrons carried by NADPH
NADP+ + H+
Pc
1 1/2 O2
4 H+
To
Calvin
Cycle
Thylakoid
membrane
STROMA
(low H+ concentra9on)
ATP
synthase
ADP
+
P i

Matrix
ADP + P i
Thylakoid
space
Thylakoid
membrane
ATP
synthase
THYLAKOID SPACE
(high H+ concentra9on)
3
NADPH
Pq
ATP
H+
ATP and NADPH are produced on the side facing the stroma, where
the Calvin cycle takes place
In summary, light reac8ons generate ATP and increase the poten8al
energy of electrons by moving them from H2O to NADPH
Carbon enters the cycle as CO2 and leaves as a

sugar named glyceraldehyde-3-phosphate
(G3P)
For net synthesis of 1 G3P, the cycle must take
place three 8mes, xing 3 molecules of CO2
The Calvin cycle has three phases:
Carbon xa9on (catalyzed by rubisco)
Reduc9on
Regenera9on of the CO2 acceptor (RuBP)
Input 3
CO2
Input 3
(Entering one
at a 9me)
CO2
(Entering one
at a 9me)
Phase 1: Carbon xa9on
Rubisco
Rubisco
3 P
Short-lived
intermediate
3 P
Ribulose bisphosphate
(RuBP)
3 P
Short-lived
intermediate
6
P
3-Phosphoglycerate
3 P
(RuBP)
6
P
3-Phosphoglycerate
ATP
6 ADP
Calvin
Cycle
6 P
P
1,3-Bisphosphoglycerate
6 NADPH
6 NADP+
6 P i
6
P
Glyceraldehyde-3-phosphate
(G3P)
1
Output
Input 3
CO2
(Entering one
at a 9me)
Rubisco
3 P
(RuBP)
6
P
3-Phosphoglycerate
ATP
6 ADP
3 ADP
3
Calvin
Cycle
6 P
P
1,3-Bisphosphoglycerate
ATP
Phase 3:
Regenera9on of
the CO2 acceptor
(RuBP)
6 NADPH
6 NADP+
6 P i
P
5
G3P
6
P
Glyceraldehyde-3-phosphate
(G3P)
1
Output
P
G3P
(a sugar)
Glucose and
other organic
compounds
Alterna8ve mechanisms of carbon

xa8on occur in hot, dry climates
3 P
Short-lived
intermediate
P
G3P
(a sugar)
Phase 2:
Reduc9on
Glucose and
other organic
compounds
Phase 2:
Reduc9on
Dehydra8on is a problem for plants, some8mes

requiring trade-os with other metabolic
processes, especially photosynthesis
On hot, dry days, plants close stomata, which
conserves H2O but also limits photosynthesis
The closing of stomata reduces access to CO2
and causes O2 to build up
These condi8ons favor a seemingly wasteful
process called photorespira8on
Photorespira8on: An Evolu8onary Relic?

In most plants (C3 plants), ini8al xa8on of CO2,
via rubisco, forms a three-carbon compound
In photorespira9on, rubisco adds O2 instead of
CO2 in the Calvin cycle
Photorespira8on consumes O2 and organic fuel
and releases CO2 without producing ATP or
sugar
Photorespira8on may be an evolu8onary relic

because rubisco rst evolved at a 8me when the
atmosphere had far less O2 and more CO2
Photorespira8on limits damaging products of
light reac8ons that build up in the absence of
the Calvin cycle
In many plants, photorespira8on is a problem
because on a hot, dry day it can drain as much
as 50% of the carbon xed by the Calvin cycle
C4 Plants
C4 plants minimize the cost of photorespira8on by
incorpora8ng CO2 into four-carbon compounds in
mesophyll cells
This step requires the enzyme PEP carboxylase
PEP carboxylase has a higher anity for CO2 than
rubisco does; it can x CO2 even when CO2
concentra8ons are low
These four-carbon compounds are exported to bundlesheath cells, where they release CO2 that is then used
in the Calvin cycle
The C4 pathway
C4 leaf anatomy
Photosynthe9c
cells of C4
plant leaf
Mesophyll
cell
Mesophyll cell
CO2
PEP carboxylase
Bundle-
sheath
cell
PEP (3C)
ADP
Oxaloacetate (4C)
Vein
(vascular 9ssue)
Malate (4C)
Stoma
Bundle-
sheath
cell
ATP
Pyruvate (3C)
CO2
Calvin
Cycle
Sugar
Vascular
9ssue
CAM Plants
Some plants, including succulents, use
crassulacean acid metabolism (CAM) to x
carbon
CAM plants open their stomata at night,
incorpora8ng CO2 into organic acids
Stomata close during the day, and CO2 is
released from organic acids and used in the
Calvin cycle
The Importance of Photosynthesis: A

Review
The energy entering chloroplasts as sunlight gets
stored as chemical energy in organic compounds
Sugar made in the chloroplasts supplies chemical
energy and carbon skeletons to synthesize the
organic molecules of cells
Plants store excess sugar as starch in structures
such as roots, tubers, seeds, and fruits
In addi8on to food produc8on, photosynthesis
produces the O2 in our atmosphere
Sugarcane
C4
Mesophyll
cell
Bundle-
sheath
cell
Organic acid
Pineapple
CO2
1 CO2 incorporated
into four-carbon
organic acids
(carbon xa9on)
CO2
Calvin
Cycle
CAM
CO2
Night
Organic acid
CO2
2 Organic acids
release CO2 to
Calvin cycle
Day
Calvin
Cycle
Sugar
Sugar
(a) Spa9al separa9on of steps
(b) Temporal separa9on of steps

1. Describe the structure of a chloroplast
2. Describe the rela8onship between an ac8on
spectrum and an absorp8on spectrum
3. Trace the movement of electrons in linear
electron ow
4. Trace the movement of electrons in cyclic
electron ow
5. Describe the similari8es and dierences

between oxida8ve phosphoryla8on in
mitochondria and photophosphoryla8on in
chloroplasts
6. Describe the role of ATP and NADPH in the
Calvin cycle
7. Describe the major consequences of
photorespira8on
8. Describe two important photosynthe8c
adapta8ons that minimize photorespira8on

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Lecture

#1: Biology & Water

Bio 1A: Introduc/on to Biology

Text: BIO 1A/B

Doudna oce hours

The chemistry of life

Chemical Founda/ons of Life

Elements, Compounds, Molecules

Elements, Compounds, Molecules

Ma]er is made up of elements

Ma]er is made up of elements

Salt is safer than the sum of its parts

Essen/al Elements of Life

The Biochemical Periodic Table

Iodine deciency: Goiter!

Water: The Molecule That Supports All of Life

The polarity of water molecules results in hydrogen

Water is the biological solvent on Earth

The water molecule is a polar molecule:

Four proper/es of water contribute to Earths

Ability to moderate temperature

Cohesion and Adhesion

Protons dissociate between water molecules

Cohesion helps the transport of water against

The pH scale is logarithmic and describes the

Units of temperature and energy

The Calories on food packaging are actually

Biological building blocks:

Biological building blocks:

Lecture #2: Biological polymers

Overview: The Molecules of Life

Larger units of the cell:

Be familiar with the contents of Figure 3.2 in your book!

Carbohydrates as fuel and building material

Carbohydrates include sugars and the polymers of

2 monosaccharides linked together by

Long chains of monosaccharides

This is an example of a condensaCon reac>on, in which two molecules

Plants use starch

The chemical formula for glucose is C6H12O6.

Lipids: a diverse group

Glycerol is a three-carbon alcohol with a

A faNy acid consists of a carboxyl group

Proteins have many structures,

Proteins adopt many func>ons via

Amino acids are organic

Protein Structure and Func>on

A func>onal protein consists of one or more

A ribbon model of lysozyme

Four Levels of Protein Structure

Examples of Quaternary Structure

A space-lling model of lysozyme

note the extensive hydrogen bonding

Nucleic acids store and transmit

There are two types of nucleic acids:

The amino acid sequence of a polypep>de is

Genes are stored as DNA, a nucleic acid

The Structure of Nucleic Acids

The Central Dogma