Important topics in cell biology

• Cell theory
• Cell structure
• Functions of specific organelles
• Membrane transport*
• Energy transduction*
• Cell-cell signalling*
• Cell cycle and its regulation

• Items marked with * are what I consider to be the

most important topics in physiology.
 Cell Form and Function
• The cell theory (pg. 90):
• 1. all organisms are composed of cells and cell
products.
• 2. The cell is the simplest structural and functional
form of life.
• 3. An organism’s structure and all of its functions are
ultimately due to the activities of cells.
• 4. All cells arise from pre-existing cells.
– All cells are descendents of the original cells.
• 5. Because of this common ancestry, all cells share
many fundamental similarities and metabolic
mechanisms.
Functions of molecules are
based on properties of atoms.

Functions of organelles are

based on properties of
molecules.

Functions of cells are based on

properties of organelles.

Functions of tissues and

organs are based on properties
of cells.
 There are about 210 cell types.
Examples include:
• Epithelial cells of diverse function
• Muscle cells
• Neurons and neuroglia
• Stem cells
• Osteocytes
• Fibroblasts
• Plasma cells
• Red blood cells
• Photoreceptor cells: rods and cones
• Hair cells
 Parts of the cell
• Plasma membrane

• Nucleus (contains genetic material; covered in Ch. 4)

• Cytoplasm (intracellular fluid; ICF)

– Contains:
• Organelles
• Cytosol
• Cytoskeleton
The plasma (cell) membrane
The Nucleus
 Cytoplasm

Organelles
Cytosol
Cytoskeleton
 The plasma membrane.
• separates inside from outside
– Different intracellular and extracellular
solutions
• Adjustable; properties vary with cell type.
• selectively permeable: it determines what
and when materials move into or out of the
cell.
The plasma membrane is a
phospholipid bilayer
Structure of phospholipids
The membrane also contains proteins, cholesterol, etc. It
has a carbohydrate coat on the outside and a cytoskeletal
support on the inside.
Transmembrane proteins
 Other components of the plasma
membrane
• Lipoproteins

• Glycolipids and
Glycoproteins
– glycocalyx
Functional categories of membrane proteins 1:
Functional categories of membrane proteins 2:
 The membrane potential
• Potential = electrical change difference.

• The membrane potential is the electrical charge

across the membrane.

• Important in membrane transport; its maintenance

consumes much of the energy we use.
 Membrane transport

Selective permeability:
Some solutes have high movement rates
Some solutes have very low movement rates.

• Movement depends on:

– the nature of the solute.
– The nature of the membrane.

• In many cases movement can be regulated by the cell

• Membrane selectivity is due to:

• Solubility of the solute in the plasma membrane.

• Presence of transporters and channels.

• The most important features of transporters are:

– their selectivity

– their ability to regulate flux.

• by opening or closing pathways.

• by use of energy to move a substance against its

concentration gradient.
 Sources of energy for transport
• Hydrostatic pressure
• Concentration gradients
• Membrane potentials
• ATP
 Methods of movement across a
membrane:
1. Passive
2. Active

3. Carrier-mediated
4. Not carrier-mediated.
 Methods of movement across a
membrane:
• Filtration
• Diffusion and osmosis
• Facilitated diffusion
• Active transport
• Secondary active transport
• Endocytosis and Receptor-mediated endocytosis
• Exocytosis and Secretion
 Filtration:
• Particles are driven through a selectively
permeable membrane by hydrostatic
pressure:
– force on a membrane due to water.
 Diffusion
• Passive
• Movement by random thermal
motion of suspended or dissolved
particles.
• Particles move from regions of
higher concentration to regions of
lower concentration.

– For living things, diffusion is :

– Adequate for movements of a
millimeter or less.
– Inadequate for movements
above this distance.

– For greater distances, bulk flow

is required
 Concentration gradients
• A concentration gradient is a source of energy.

• Movement up a concentration gradient.

– Requires energy; creates a secondary source of
energy that can be used for other things.

• Movement down a concentration gradient.

– Does not require energy. Instead it releases
energy that can be used for other things.
 questions
• How is a concentration gradient a source of
energy?

• What is equilibrium?
 Factors influencing the rate of
diffusion include:
• Temperature
• Molecular weight
• The concentration gradient

• If there is a membrane:
– Membrane surface area
– Membrane permeability
 Transport of water
• Water moves across many membranes.

• It is not believed that specific water pumps exist.

• Instead, water moves across cell membranes by:

1. osmosis: following movement of solutes,
passing through the membrane primarily in pores
called aquaporins.
• 2. hydrostatic pressure.
Hydrostatic pressure
 Osmosis: diffusion of water
• Diffusion of water across
a semipermeable
membrane

• Osmotic movement of
water creates hydrostatic
pressure.

• Osmotic pressure: the

measured hydrostatic
pressure required to
oppose movement by
osmosis.
 Osmotic pressure:
• Due to the concentration of solute particles.

• Osmole: 1 mole of solute particles

– Does the substance dissociate?
– 1 mole of NaCl dissociates to form 2 moles
of particles.

• Osmolarity: number of osmoles per liter of

solution.
• 1 osm/L = 1 mol/L of particles
 Osmoticity
• Isosmotic: solutions that exert the same osmotic pressure.
– “Normal saline”: 0.9% NaCl has a solute concentration that
equals that of body fluids

• Hypoosmotic: a solution that exerts less osmotic pressure with

respect to another.
– More dilute

• Hyperosmotic: a solution that exerts more osmotic pressure

with respect to another.
– More concentrated
Osmosis at the molecular level
 Tonicity: refers to what happens
to a cell in a solution.

Tonicity is not always equivalent to osmotic pressure

When is iso-osmotic not isotonic?
 Steady state conditions
• Solutes are always moving across the membrane.

• Concentrations of solutes are different inside and

outside the cell.

• Concentrations remain relatively constant over time.

– At equilibrium, no forces drive movement.
– At steady state, net movement is zero but the
substance is not (necessarily) at equilibrium.
 Ionic steady state:
• Concentrations of ions remain relatively
constant inside and outside the cell.
– Levels of particular ions may be very
different in ICF and ECF.

• Example: Na+ and K+ concentrations are

different inside and outside the cell.

• Maintained at steady state conditions.

• Na+ concentrations especially are far

from equilibrium yet remain constant
over time.
– Requires input of energy.
Separation of electrical charges is called a voltage or
potential.
This causes current flow.
Voltages and Current flow in aqueous solutions are due to
distributions and movements of ions.

An electrical potential is a source of energy.

V = IR
 The membrane potential
• The electrical charge across the cell membrane.

• Inside negative, outside positive.

 Influences on ion distribution.
• The concentration gradient.
• The electrical potential (voltage).

• The sum of the forces due to these two

factors is called the electrochemical
gradient.
 The equilibrium potential:
• The voltage at which the driving force due to a
concentration gradient is exactly balanced by the
electrical driving force (voltage).

• Concentration may drive an ion in one direction,

voltage in the other.
• No energy is available to drive movement because
one source of energy is cancelled by another leaving
a net energy of zero.
 Active vs. passive transport
• Active- input of energy is required.
– Movement is uphill.

• Passive- energy is present in the form of an

electrochemical gradient.
– Note: the gradient may have required energy to
create and maintain. However, the movement of
the substance in question is driven by the
electrochemical gradient.
 Routes for passive movements:
A.
Diffusion across the
lipid membrane

B.

Diffusion through protein

channels.
C.
Carrier mediated
Transport.
A. Diffusion across the lipid membrane
 B. Diffusion through membrane channels.

• Charged molecules cross

membranes through water-filled
channels.
• These are integral membrane
proteins.

• highly specific, can be blocked

(many pharmacological
compounds act in this way).

• Some are gated channels

– Ligand gated
– Voltage gated
– Mechanically gated.
 C. Facilitated diffusion; carrier
mediated transport

It is diffusion requiring interaction with a specific protein

Carrier mediated transport is saturable
 Active transport:
• All living cells expend energy to maintain
significant electrochemical gradients of a number of
solutes across cell membranes.
– Regulate extracellular fluids
– Regulate intracellular fluids

• This requires moving solutes uphill.

• Energy is provided in the form of ATP.

• Proteins that actively transport substances up a

membrane gradient are called membrane pumps, or
pumps.
 Primary vs secondary active transport.
• Primary: ATP is used to create an electrochemical gradient.

• Secondary: Downhill movement of one solute is coupled

with uphill movement of another.
– A wide variety of solutes are transported using energy
from the Na+ electrochemical gradient across the cell
membrane
• created by the Na/K ATPase and regulation of ECF Na+ by the
kidneys.
 The Na/K ATPase (pump)
• The gradients of Na+ and K+
across the membrane are
created and maintained
primarily by the Na/K
ATPase.

• The concentration gradient

is determined by
– the rate of Na+ and K+
export and leak.
– regulation of
extracellular fluid
composition.
• At steady state, the rate of
Na+ extrusion equals the rate
of influx.
 Roles of the Na/K ATPase
• A critical role in creation and maintenance of the
membrane potential.

• Regulation of cell volume.

• Creation of gradients that drive secondary active

transport.

• Heat production.
Generation of the membrane potential
• Most important contributions:
• Na+ and K+ electrochemical gradients.

Na/K ATPase.
Leak channels.
Kidneys etc. regulate extracellular Na+ and K+
concentrations.
 Types of carrier proteins involved in
facilitated diffusion and coupled transport:
• Uniporters: carry a single
solute across the membrane.
• Coupled transporters:
transfer one solute, and
simultaneously or
sequentially transfer another.
– Symporters: transfer
solutes in the same
direction.
– Antiporters: transfer
solutes in opposite
directions.
Secondary active transport driven by Na+
gradients

+ charge

- charge
Powering glucose
uptake with the
Na/K ATPase.
 Bulk transport:
• Phagocytosis: cell eating- ingestion of solid
particles

• Pinocytosis: cell drinking- ingestion of fluid

– Both involve a similar process of pinching

in a portion of the plasma membrane.
Receptor mediated endocytosis
Figure 3.23
 Transcytosis
• Transport of a substance across a cell by
phagocytosis at one side and exocytosis at
the other.
 Organelles:
• Specialized
structures with
characteristic
shapes and
functions.

• Number and type

depends on cell
type.
 Types of organelles:
• Nonmembranous:
– Cytoskeleton, centrosomes, and ribosomes.

• Membranous:
– Nucleus, endoplasmic reticulum, Golgi
complexes, mitochondria, lysozomes,
peroxisomes.
The nucleus:
Endoplasmic reticulum
 Ribosomes
• Translate genetic information
from RNA to a sequence of
amino acids in a protein.
• Free ribosomes: free in the
cytoplasm; make proteins to
be used in the cell.
• Membrane-bound ribosomes:
make proteins to be exported
or inserted into plasma
membrane.
• Mitochondrial ribosomes:
make mitochondrial proteins.
 Golgi complex:

Synthesize carbohydrates.

Receives proteins from rough

ER and completes the
process of protein and
glycoprotein manufacture

Form golgi vesicles, secretory

vesicles, lysosomes, etc.
Figure 3.27
 Lysosomes
• Remain within cell, contain
many enzymes
• Digest things within the cell-
– Autophagy: worn out
organelles
– Autolysis: Programmed
cell death
– Ingested bacteria

Tay-Sachs disease: due to

the absence of a single
lysosomal enzyme.
Lysosomes and peroxisomes

Figure 3.28
 Mitochondria
Figure 3.29
A double membrane
with an intermembrane
space

Extensions of the
membrane called crista
extend into the matrix.

The matrix fills the

inside.
Centrioles
 Cytoskeleton
• A network of protein
filaments providing support
and movement

• 3 types of protein filaments

– Microfilament

– Intermediate filament

– Microtubule
MICROFILAMENT INTERMEDIATE MICROTUBULE
FILAMENT
 Microfilaments

• Formed of actin.

• Form the membrane

skeleton.
• Important in muscle
cell contractions.
Microvilli: non-motile extensions of the
cell membrane involved in transport
 Microtubules

• Formed of tubulin

• Form cilia and flagella,

etc..
 Cilia and flagelli: motile
extensions of the cell membrane
• Cilia: relatively short, many
per cell, move material past
a stationary cell.

• Flagelli: relatively long,

one or two per cell (in
humans, only the sperm
have one), move the cell
through fluid.
Figure 3.11
 FLAGELLUM

Electron micrograph
of sections:

Outer microtubule
doublet

Plasma
membrane

Flagellum

Central
microtubules

Outer microtubule
doublet

Plasma Basal body

membrane
Basal body
(structurally identical to centriole)
• Microtubules with dynein motor proteins drive the
whipping action of the cilia and flagella.

Microtubule doublet

Dynein arm Sliding

force
 Chapter 26

Energy transduction: formation of ATP

 The importance of ATP
• ATP is an Energy Coupler:

• Energy is released by breakdown of complex

molecules, and captured in ATP.

• ATP is then used for everything the cells do that

requires energy, including movement, maintenance of
concentration gradients across membranes, active
transport across membranes, synthesis reactions etc.
ATP is hydrolyzed to ADP, releasing
energy that can by used by cellular
processes.

Adenine
Phosphate
groups
Hydrolysis
Energy
Ribose
Adenosine triphosphate
Adenosine diphosphate
(ADP)
 Production of ATP
• Energy is released from breakdown of complex
molecules such as glucose.

• Some of this energy is captured in the form of

ATP.
– Aerobic metabolism: food molecules are
oxidized completely to CO2 and H2O using
oxygen as a final electron acceptor.
– Anaerobic metabolism: food molecules are
oxidized incompletely to lactic acid.
3 major pathways of glucose catabolism:
• Glycolysis: breakdown of glucose to two pyruvic
acid molecules.

• Then, either one or the other of the following

occurs:
• Anaerobic fermentation: when O2 is not present
reduction of pyruvic acid to lactic acid occurs.

• Aerobic respiration: when O2 is present oxidation

of pyruvic acid to CO2 and H2O occurs.
 Oxidation-reduction reactions:
• Electrons don’t exist free in solution. They must be
transferred from one compound to another.

• Oxidation is loss of an electron

– Oxidant: electron acceptor

• Reduction is gain of an electron

– Reductant: electron donor

• Every physiological oxidation-reduction reaction

involves simultaneous oxidation of one molecule and
reduction of another.
 It is hard to count electrons, so:
• Electrons in biological redox reactions are
associated with transfer of specific atoms.

• Electrons are generally carried as a proton plus an

electron (a hydrogen atom).

– Oxidation: usually gain of O or loss of H.

– Reduction: usually loss of O or gain of H.
 Coenzymes: electron carriers

• FAD + 2 H+ + 2 e-  FADH2
• NAD+ + 2H+ + 2e-  NADH + H+

• Electrons start out in glucose and wind up being

transferred to oxygen, forming H2O.
– Glucose is oxidized, oxygen is reduced.

• The carbons of glucose wind up in CO2 molecules.

Cellular respiration: The aerobic oxidation of
glucose to produce ATP involves 4 sets of
reactions:
 
1) Glycolysis

2) Formation of acetyl coenzyme A

 
3) Krebs (Citric acid) cycle
 
4) Electron transport chain and chemiosmosis
• Glycolysis (Anaerobic respiration): 2 moles of
ATP are produced per mole of glucose (about 2%
of the energy is captured).

– Occurs in the cytosol!

• Aerobic respiration: 38 moles of ATP per mole of

glucose (about 42% of the energy is captured).

– Occurs in mitochondria!
Aerobic metabolism occurs in two separate steps,
located in different parts of the mitochondion

• The Matrix reactions: Glucose is oxidized in a

series of steps to form CO2.
– Electrons are captured in coenzymes which
then take them to the electron transport chain.

• The membrane reactions: the electrons pass

through an electron transport chain.
– a series of redox reactions ending in oxygen,
forming H2O.
Formation of acetyl coenzyme A
The Krebs, or citric
acid, cycle
Oxaloacetic acid Citric acid
 Other molecules can also be fed
into the Krebs (Citric acid) cycle:
• Amino acids
• Fatty acids
• Glycerol
• Ketone bodies
The electron transport chain and
chemiosmosis
 Chemiosmosis
• The downhill flow of H+ through ATP synthase,
driving the formation of ATP.
 In the absence of oxygen:
• Electrons have no place to go.

• NAD+, a substrate of glycolysis, must be

regenerated for glycolysis to continue.

• NADH reduces pyruvic acid to lactic acid,

forming NAD+.