13 August 2019

12-1pm LT33

LSM 1106
Molecular Cell Biology

A/P Marie-Veronique Clement

bchmvc@nus.edu.sg
MD7 Level 4
Department of Biochemistry

Access to lecture notes etc. through: LumiNUS

 Organization of the module

Lectures

This module will cover fundamental concepts in

molecular cell biology, focusing on major classes of
biomolecules
Molecular biology is the study of molecular underpinnings of the processes of replication, transcription,
translation, and cellular function.

Lecturers:

A/P Marie-Veronique Lectures:

Clement
A/P Deng Lih Wen Mondays
A/P Henry Mok 4:00 - 6:00pm
 Organization of the module

Tutorials and Practicals

n Tutorials: Solve sample problems

Work on problems before coming to the tutorial.
n Practicals: Experiments related to lectures
Read the Practical Manual before the practical.

Topics covered in tutorials and practicals will be in

CAs and Exams
Tutorials:
Tuesdays 12:00 LT33
Practicals:
Fridays 10:00 - 14:00 MD7 Level 1 LS Lab 8
 Organization of the module

Practicals

n Please read safety slides (“Safety” folder) and make

the online safety declaration (Available through
LumiNUS go to “tools” under “assessment”)

n Please make sure to come with proper clothing and lab

coat

YOU WILL NOT BE ALLOWED TO TAKE PART IN

THE PRACTICALS IF YOU HAVE NOT DECLARED
OR DO NOT HAVE PROPER ATTIRE

IMPORTANT
 Organization of the module

Why tutorials and practicals are important?

n You need to learn how to solve problems (pH calculations,

enzyme kinetics, etc.)
n Tutorial problems
Make sure you can do
n Problems found in textbooks these before CAs and
n Problems in practicals exams

n You also need to know various facts covered in lectures,

tutorials and practicals
n Help is available if some concepts are unclear
n TAs and lecturers at practicals
n Discussion forum (TAs and other students)
n Lecturers (Tutorials/After lecture/Consultation)
 Organization of the module

Assessment

CA1: 20%
CA2: 20%
Examination: 60%

CA and exam – Short answer questions (SAQs)/ Multiple

choice questions (MCQ)
(MCQs)

Consult the timetable and LumiNUS for update

CA/Examination time and venue.
 Organization of the module

Recommended text

Other editions or similar textbooks are also ok.

e.g. Voet, Voet and
n Garrett & Grisham. Biochemistry Pratt
n Lodish et al. Molecular Cell Biology
n Alberts et al. Molecular Biology of the Cell
 Because Molecular biology is the study of molecular underpinnings of the
processes of replication, transcription, translation, and cellular function.
Lets first check what is a cell:

What is a Cell?

https://www.youtube.com/watch?v=Ta_zGRHGaHw
Everything You Need to Know about CELLS - Mfilms EDU
8:14min
 Cells makes YOU but What are cells made of?

Figure 1-30 Molecular Biology of the Cell, Fifth Edition (© Garland Science 2008)
 Cells are made of different classes of
biomolecules

Four classes
of
biomolecules
 Cells are made of different classes of
biomolecules also known as macromolecules
n Proteins
n Enzymes
n Structural proteins (membranes)
n Regulation and signaling
n Nucleic acids
n Information storage
n Lipids
n Structural (membranes)
n Regulation and signaling
n Energy storage
n Carbohydrates
n Structure and molecular recognition (Extracellular region)
n Energy storage
 Where do you find macromolecule in the cell?
Cell surface membrane as an example

Lipids
Proteins
 Cell functions are regulated by
signals transduction

Proteins
Nucleic acids:
DNA/RNA

Figure 15-6 Molecular Biology of the Cell (© Garland Science 2008)

 Signaling pathway in the cytosol and nuclear components
(One of the many examples only)

ligand Protein –
receptor
lipid binding Enzyme-
substrate action
Ras
Grb2 Ser
Kinase
phosphorylation
Sos Raf at S/T/Y aa
Ser
MEK
Thr/Tyr
Y P MAPK
Thr/Ser
Y P c-Myc

Protein-Protein Grb2 Nucleus

Sos Protein-DNA
Interactions
interaction
 Organization of a cell

Gobular vs filamentous actin

proteins

Polymerisation

Depolymerisation

(A) Globular actin (G-Actin) monomer versus (B) Filamentous Actin (F-Actin)
Figure 16-12 Molecular Biology of the Cell (© Garland Science 2008)
 Cells shape
Cytoskeletal actin is dynamic

Actin Microtubule DNA

Filamentous actin
Changes in cell shape
Maintains cell shape
involves cycles of
polymerisation and
Figure 16-1, 2 Molecular Biology of the Cell (© Garland Science 2008) depolymerisation
 Summary so far

1.Cellular Structures are composed of various

macromolecules (protein, lipids, carbohydrates)

2.Molecular forces are important in maintain

cellular structures, cellular processes and
regulation of cellular activities
 Cell as a universal feature of life

Break

https://www.youtube.com/watch?v=pJqfmuuxNXs
Macromolecules-A Beginners Guide
2:40min
Before we explore further what are the structure and properties of
macromolecules, we need to do a bit of chemistry.

Water: the essential solvent of life

Behavior of molecules in water

 Water

Importance of water in biochemistry

n Properties of biological molecules depend on

the fact that they are in a water environment

Biomolecules
(proteins, DNA, etc.)

Cell
Mostly water

In other words, many biological molecules do not

function when they are not in the aqueous (water)
environment
 Water
Water is polar (meaning parts of the
molecule contain weak + and – charges)

Weak negative charge

Non-bonding electrons on O causes partial
d- negative charge on O and partial positive

O
charge on H.

H H
d+ d+
Weak positive charge
 Water has the ability to form hydrogen bonds
(H-bond)
O
Bond (attraction)
Water between partial
H H charges.
d- d+
The hydrogen bond is
O a weak bond and can
be broken easily.
H H Covalent bond
d+ d+ d- (hundreds of kJ/mol)
O
Hydrogen bond
(< hundred kJ/mol)
H H
Ice (solid water) has a rigid structure
Water

held together by H-Bonds

Red atoms = Oxygen

 Water
In liquid water, hydrogen bonds are
transient

Because water
molecules move
around, no large-scale
structure exist.

Bonds are being made

and broken constantly.
Solute and solvent

• A solvent is a liquid that dissolves a solid, liquid or gaseous

solute.

• A solute is a substance dissolved in another substance.

• A solute and a solvent make up a solution.

• The solute is usually present in a smaller amount than the

solvent.
 Solutions

Different types of solutes

n Ionic compounds
n Polar molecules
n Non-polar molecules

These compounds have different

solubility in water (solvent) because
they interact with water in different
ways.
 Hydrophobic vs. hydrophilic molecules

n Hydrophilic (= water loving) molecules dissolve

easily
n Relatively strong interaction with water
(including H-bonds)

n Hydrophobic (= water fearing) molecules do not

dissolve easily
n Relatively weak interaction with water
 Ionic solutes

Ionic compounds

Cl- Na+ Cl- Na+ Cl- Na+

Na+ Cl- Na+ Cl- Na+ Cl-

Cl- Na+ Cl- Na+ Cl- Na+

Ionic compounds are composed of positive

and negative ions.
e.g. NaCl = table salt
 Ionic compounds dissociate in wate r Io nic solutes

if dissolved
d+ d+ d- O
H H
H H
O d- d+ d+
d+ H H d+ H d+ d+ H

Cl-
d-
Na+
d-
O O O O
d- d-
d+ H H d+ H d+ d+ H
d- O d+ d+
H H
H H
d+ d+ O d-

Water arrange to form hydration shells around charged

molecules (ions) -> favorable electrostatic interactions

Within salt water, Na+ and Cl- exist in these forms

 Polar solutes

Polar molecules

d-

d-
d+

C6H12O6
Glucose
Polar molecules contain groups that carry partial
charges (similar to H2O) and can form hydrogen
bonds: e.g. -OH, -NH2, C=O
 Polar solutes
Polar molecules are hydrophilic
(like water)
d- O d- O

H H d- H H
d+ d+ d+
d+

d-
+
d
H

d- O
d+
d+
H

d+ d+
H H

d- O Glucose
Polar molecules form hydrogen bonds with water
and are hydrophilic
(strong interaction between water and solute)
 Polar solutes
Many biological molecules are
hydrophilic

polar
sugar groups

amino ionic
acids groups

sugar
 Non-polar solutes

Nonpolar compounds (do not like water)

Propane

No hydrogen bonds (not polar)

(CH groups do not form H-bonds)
Not ionic

Do not interact (e.g. H-bond) with water

Non-polar molecules are hydrophobic
 Water forms the clathrate (cage like)
structure around nonpolar solutes

Clathrate
formation

When non-polar molecules are in water, they cause water

molecules to form clathrates (cage-like arrangement of
water molecules around non-polar solutes)

Clathrate formation is generally not favored, so it s

difficult for non-polar molecules to dissolve
 Non-polar solutes

Hydrophobic interaction

Hydrophobic molecules are attracted to each other in water,

since coming together reduces the surface area exposed to
water
This attraction is called hydrophobic interaction
 Non-polar solutes

Hydrophobic interactions occur...

n ... not because non-polar molecules are strongly

attracted to each other on their own.

n ... because of the tendency to minimize

water/hydrophobic interaction (to minimize
clathrate formation).

This means that hydrophobic interaction occur only in

aqueous environment.

Hydrophobic interaction would not be observed in non-polar

solvents.
 Different types of solutes (summary)

n Ionic compounds
n Hydrophilic
n Forms hydration shells
n Polar molecules
n Hydrophilic
n Forms hydrogen bonds with water
n Non-polar molecules
n Hydrophobic
n Attracted to each other in water
n Forms clathrates
 Molecules with hydrophilic & hydrophobic
parts are called Amphipathic (amphiphilic)

(a component of cell membrane)

Hydrophobic Hydrophilic

Attracted to other Attracted to water

hydrophobic molecules
 A m ph ipat hi csolutes
Amphipathic molecules can form co m plex
structures, and are important in cells
Micelles
Polar surface
Typical cell
exposed to the
membrane lipids water environment
Hydrophilic end

Non-polar groups
attract each other

Hydrophobic
end
Cell
membrane
 Proteins
Proteins typically contain a hydrophobic
core surrounded by hydrophilic surface

Hydrophobic core
(shielded from water)

Hydrophilic surface

Hydrophobic interaction (attraction between hydrophobic groups)

keeps the protein folded, while hydrophilic groups on the surface make
the protein soluble.
This will be discussed in more detail when we discuss protein folding
 Detergents
Detergents (soaps) are amphipathic compounds

Non-polar Ionic
Hydrophobic Hydrophilic
Detergents make
hydrophobic OSO3- Na+
substances soluble
(Sodium) dodecyl sulfate
Also called lauryl sulfate

(look for it in your favorite

shampoo, toothpaste, etc.)
 Summary so far

1.Water is important in influencing

behavior of biological molecules

2. Biological molecules: Ionic, polar, non-

polar
https://www.youtube.com/watch?v=njWsfApthXc
Properties of Water | Hydrogen Bonding in Water | Biology | Biochemistry
12:36min Published on Jun 26, 2017
 Water dissociation

H2O dissociates into H+ and OH-

H2 O H+ + OH-
Any aqueous solution contains H2O, H+, and OH- in a
state of equilibrium

n Many biochemical processes occur only at certain

concentrations of H+ ions in solution.
n The concentration of H+ is described by pH
In water:
Definition: pH = - log10[H+]
[H+]=1X10-7
[H+] = molar concentration of H+ pH = - log10[1X10-7]
= moles/liter of H+
=7
Next lecture we will revise our

Acid/base chemistry

See you next week