Biochemistry

Power to Understand
What We Are!!
 Learning objectives
At the end of this session the students will be able to:-

 List the major chemical elements of life.

 Explain the significance non-covalent interactions.

 Discuss the properties and role of water.

 Describe acid-base balance and role of buffers.

 Explain the roles of carbohydrates and its classification.

 Outline
 Common elements of life

 Important functional groups and non-covalent

interactions.

 Water and acid-base balance, buffers

 Carbohydrate structure: monosaccharides, sugar

derivatives, disaccharides and polysaccharides.
 Chapter 1. Introduction to Biochemistry
 The word ‘Biochemistry’- means -
Chemistry of Living things or
Chemical Basis of Life.

 The word biochemistry was first

introduced by a Germen Chemist,
Carl Neuberg in 1903.
“Chemistry of Life”
 ‘’Life” in Biochemistry point of
view is:
 Hundreds of Biochemical reactions
and Biochemical processes
occurring in sub cellular
organelles of a cell in an organized
manner.
 1.1 Biochemistry
 Definition: The chemistry of life
 The science concerned with:

the chemical basis of life.

the various molecules that occur in living
cells and organisms and with their
chemical reaction.

 Anything more than a superficial

comprehension of life – in all its diverse
manifestation - demands a knowledge of
biochemistry.
 Branches of Biochemistry
 Biochemistry emerged in the late 18th and
early 19th century.
 Medical Biochemistry-Deals with chemical
basis of human body.

 In the 1940s Clinical Biochemistry evolved,

as an autonomous field.

 Clinical Biochemistry-Deals with clinical

diseases/pathological conditions of human
body.
Clinical Biochemistry supports:
Diagnosis, Therapy and Research of Medical
field.
 Aim And Objectives To Study
Biochemistry
 To know the various Biomolecules
composed in Human body:

Chemistry/Structure

Occurrence/Location

Functions/Role

 Determination of mode of action of

Biomolecules is by:
 Isolation and Structural elucidation of
Biomolecules.
 Aim And Objectives To Study
Biochemistry
 Understand completely all the
organized Biochemical processes,

Occurring in living cells at the
molecular/sub cellular level .

 Identification of disease mechanisms:

 Study of Inborn Errors of metabolism.
 Study of Oncogenes in cancer cells.
 Course Syllabus of Biochemistry
Medical Biochemistry
 Medical or Human Biochemistry is a
branch of Biochemistry which deals with:
 Biochemical constituents of human
body,

 Their interactions in body cells,

 To maintain normal health, growth and

reproduction and related diseases.
Catabolic and Anabolic pathways related
to Biomolecules for Human Vitality
 Energy rich biomolecules get catabolized in
body cells to liberate chemical form of energy
ATP used for various body activities.

 Various biomolecules are biosynthesized to

perform vital functions of human body.

 To maintain normal health of a human body:

 Biomolecules in human body work Cooperatively
with good coordination, Regulation and
Interrelationship.
 Interrelationships of Biochemistry

 Biochemistry Is A Fundamental Subject of Medicine/Health Sciences

 Biochemistry is related to almost every Subject of Medicine.
 There is relationship of Biochemistry with Many
subjects of Medicine/Health Sciences.
 Physiology
 Pathology
 Pharmacology
 Immunology - Microbiology
 Toxicology
 Medicine and Allied Subjects
 Community Medicine-Nutrition
 Genetics
 Importance of Biochemistry
Knowledge To A Doctor/Health Science
Professionals
 Clear understanding concepts of
Biochemistry Is a prerequisite to become A
Good Doctor/Health Science Professional.

 A thorough understanding knowledge, of

Biochemistry by a Doctor/Health Science
Professional helps in:

Right Diagnosing and treating a patient.
 Role/Importance of Clinical
Biochemistry Laboratory Tests

 Results of Biochemical investigations plays

important role in screening, diagnosis,
prognosis and treatment of disorders.

 A good understanding Knowledge of

Biochemistry related to health and disease at
molecular level
 Makes a true and good Doctor for his/her
Clinical Practice.
 1.2 Organization of Life
• Elements
• Simple organic compounds (monomers)
• Macromolecules (polymers)
• Supramolecular structures
• Organelles
• Cells
• Tissues
• Organisms
 Elements
• Substances that can not be broken down into simpler substances
by chemical reactions.
• There are 110 different elements that are known to man.

• Life requires about 25 of them.

• The living matter is composed of mainly six elements:

– Carbon, Hydrogen, Oxygen, Nitrogen, Phosphorus and Sulphur.(CHONPS).
– These elements together constitute more than 90% of the dry weight of the
human body.

• Several other functionally important elements are also found in

the cells.
– These include: Ca, K, Na, Cl, Mg, Fe, Cu, Co, Zn, F, Mo and Se.
 Carbon-a unique element of life
• Carbon is more abundant in living organisms than it is in
the rest of the universe.

• Carbon is the most predominant and versatile element of

life.

• It possesses as unique property to form infinite number of

compounds.

• This is attributed to the ability of carbon to form:

 stable covalent bonds and C-C chains of unlimited length.

• It is estimated that about 90% of compounds found in

living system invariably contain carbon.
Carbon can form immensely diverse
compounds, from simple to complex.

Methane with 1 DNA with tens of Billions

Carbon atom of Carbon atoms
 Structural hierarchy in the molecular organization of
cells

 Just like cells are building blocks of tissues, biomolecules

are building blocks of cells.
 1.4 Biomolecules
 Biomolecules are compounds of carbon with a
variety of functional groups.
 Just like cells are building blocks of tissues,
biomolecules are building blocks of cells.
 Animal and plant cells contain approximately
10,000 kinds of biomolecules.
 Water constitutes 50-95% of cells content by weight.
 Ions like Na+, K+ and Ca2+ may account for another
1%.
 Almost all other kinds of biomolecules are
organic (C, H, N, O, P, S).
 Organic compounds are compounds composed
primarily of a Carbon skeleton.
 Types of biomolecules
 Small molecules:
 Phospholipid, glycolipid, sterol,
 Vitamin
 Hormone, neurotransmitter
 Sugar
 Monomers:
 Amino acids
 Nucleotides
 Monosaccharides
 Polymers:
 Peptides, oligopeptides, polypeptides, proteins
 Nucleic acids, i.e. DNA, RNA
 Oligosaccharides, polysaccharides (including
cellulose)
Relatively few monomers are used by cells to
make a huge variety of macromolecules

Macromolecule Monomers or Subunits

1. Carbohydrates 20-30 monosaccharides
or simple sugars

2. Proteins 20 amino acids

3. Nucleic acids (DNA/RNA) 4 nucleotides (A,G,C,T/U)

4. Lipids (fats and oils) ~ 20 different fatty

acids

and glycerol.
 Making and Breaking
Polymers


There are two main chemical
mechanisms in the production and
break down of macromolecules.

Condensation or Dehydration Synthesis

Hydrolysis


In the cell these mechanisms are
regulated by enzymes.
 Functional Groups
• Groups of atoms that have unique chemical and physical
properties.

• Compounds that are made up solely of carbon and

hydrogen are not very reactive.

• One or more H atoms of the carbon skeleton may be

replaced by a functional group.

• Functional groups determine chemical & physical

properties of organic molecules.
Biomolecules are compounds of carbon with a variety of functional
groups

FIG. Major types of functional groups found in biochemical compounds of the human body.
 Similarities among all types of cells
 All cells use nucleic acids (DNA) to store
information

Except RNA viruses, but not true cells
(incapable of autonomous replication)
 All cells use nucleic acids (RNA) to access
stored information
 All cells use proteins as catalysts (enzymes)
for chemical reactions

A few examples of RNA based enzymes, which may
reflect primordial use of RNA
 All cells use lipids for membrane components

Different types of lipids in different types of cells
 All cells use carbohydrates for cell walls (if
present), recognition, and energy generation
Chemical composition of a normal man
(weight 65 kg)

Constituent Percent (%) Weight (kg)

Water 61.6 40

Protein 17.0 11

Lipid 13.8 9
Carbohydrat
1.5 1
e
Minerals 6.1 4
 1.5 Water

The Ideal Compound for Life


Living cells are 60-90% water


Water covers 3/4 of earth’s surface


Water is the ideal solvent for chemical

reactions


On earth, water exists as gas, liquid, and

solid
 Water
 Making up 60% or more of the weight of most
organisms.

 Biological macromolecules assume specific shapes

in response to the chemical and physical properties
of water.

 Biological molecules undergo chemical reactions in

an aqueous environment.

 Many of the weak interactions within and between

biomolecules are strongly influenced by the solvent
properties of water.
 such as membrane lipids, interact with each other in
ways dictated by the polar properties of water.
Fig.2 Fluid compartments of the body.
Volumes are for an average 70-kg person.
 Functions of Water in Human Body
 Transports nutrients and oxygen into cells
 Regulates body temperature
 Detoxifies
 Moisturizes the air in lungs
 Helps with metabolism
 Protects vital organ
 Helps organs to absorb nutrients
 Protects and moisturizes our joints 32
 Hydrolysis/ Energy Release
 Water is needed to separate (by hydrolysis) a
phosphate group from ATP or GTP to get energy.
 Without water hydrolysis is not possible.

 ATP +H2O = Energy + ADP + Inorganic

Phosphate
 GTP +H2O = Energy + GDP + Inorganic
Phosphate

 Water is the engine of metabolism.

 Participates in the biochemical break-down of
what we eat. 33
 Variation in Water Levels
Tissue type:
 lean tissues have higher fluid content than fat
tissues.
Gender:
 males
Lean have
tissue is amore
general termlean
that refers tissue
to any tissue in and therefore
the body that is not fat. more
Fat tissue, also known as adipose tissue, is a type of connective tissue that stores energy in the form of
bodytriglycerides.
fluid.It's found throughout the body, both beneath the skin (subcutaneous fat) and around internal
organs (visceral fat).
Age:
 lean tissue is lost with age and body fluid is lost
with it.
 Water
 A water molecule (H2O), is made up
of three atoms --- one oxygen and
two hydrogen.
 Polarity
 Many of water’s biological functions
stem from its chemical structure.

 Water is a polar molecule

 It has unequal charge distribution that
results in areas of δ- and δ+ charge (δ =
partial)
 The oxygen in water is more electronegative
than the hydrogen

The oxygen nucleus has a greater attraction for
electrons than the hydrogen nucleus,

so the oxygen will have a δ- charge, leaving the
hydrogen with a δ+ charge
 Polarity of water causes hydrogen
bonding

 Water molecules are held together by H-bonding

 Partially positive H is attracted to partially

negative O atom.

 Individual H bond are weak, but the cumulative

effect of many H bonds is very strong.

 H bonds only last a fraction of a second, but at

any moment most molecules are hydrogen bonded
to others.
Unique properties of water caused by H-bonds

Cohesion: Water molecules stick to each other.
This causes surface tension.

Film-like surface of water is difficult to break. The strong cohesive forces between
water molecules make it difficult to

Used by some insects that live on water surface.
break the surface tension. This is why
certain insects can walk on water.

Water forms beads. This is because the cohesive forces between
water molecules are stronger than the adhesive
forces between water and the surface.

Adhesion: Water sticks to many surfaces.

Capillary Action: Water tends to rise in narrow
tubes.

This is caused by cohesion and adhesion (water molecules stick to
walls of tubes).

Examples: Upward movement of water through plant vessels and fluid in blood
vessels.
Unique properties of water caused by H-bonds


Expands when it freezes.

Ice forms stable H bonds, each molecule is bonded
to four neighbors (crystalline lattice).


liquid Water does not form stable H bonds.

Ice is less dense than water.

Ice floats on water.


Life can survive in bodies of water, even though the
earth has gone through many winters and ice ages.

•When water freezes, it forms a layer of ice on the

surface. This layer acts as an insulating blanket,
preventing the water below from freezing solid. This
allows aquatic life to survive the harsh winter conditions.
 Lower density of ice in comparison to
liquid water
 A given mass of ice occupies a
greater volume than that of
liquid water.

 This is because of an ordered

open H-bonding arrangement
in the solid (ice) in
comparison to continual
forming & breaking H-bonds
as a liquid.
 Unique properties of water caused by H-bonds

 Stable Temperature: Water resists changes in

temperature because it has a high specific heat
capacity.
 Specific Heat Capacity: Amount of heat energy needed to
raise 1 g of substance 1 degree Celsius

Specific Heat Capacity of Water: 1 calorie/gram/oC

 High heat of vaporization: Water must absorb large amounts

of energy (heat) to evaporate.

Heat of Vaporization of Water: 540 calorie/gram.
 Evaporative cooling is used by many organisms to regulate
body temperature with heat of vaporization of water.

Sweating

Panting
 Unique properties of water caused by its
polarity

 Universal Solvent: Dissolves many (but not all)

substances.
Two Types of Solutes:
A. Hydrophilic: “Water loving” dissolve easily in
water.

Ionic compounds (e.g. salts)

Polar compounds (molecules with polar regions)

Examples: Compounds with -OH groups (alcohols).

“Like dissolves in like”

B. Hydrophobic: “Water fearing” do not dissolve

in water

Non-polar compounds (lack polar regions)

Examples: Hydrocarbons with only C-H non-polar bonds, oils,
 1.6 Weak Acids and Bases; Buffer
systems
pH = - log [H+]

H+ is really a proton

 Range is from 0 - 14

 If [H+] is high, the solution is acidic; pH < 7

 If [H+] is low, the solution is basic or

alkaline ; pH > 7
 The Body and pH
 Homeostasis of pH is tightly controlled
 Extracellular fluid = 7.4
 Blood = 7.35 – 7.45
 If pH is < 6.8 or > 8.0 death occurs
 Acidosis (acidemia) below 7.35
 Alkalosis (alkalemia) above 7.45

45
46
 Acid/conjugate base pairs

HA + H2O A- + H3O+
HA A - + H+
HA = acid ( donates H+)(Bronstad Acid)
A- = Conjugate base (accepts H+)(Bronstad Base)

Ka = [H+][A-] Ka & pKa value describe tendency to

loose H+
[HA]
pKa = - log Ka large Ka = stronger acid
small Ka = weaker acid
 Buffer Solution
 A buffer is a mixture of an un-dissociated acid
and its conjugate base (the form of the acid
having lost its proton).
 It causes a solution to resist changes in pH when
either H+ or OH- is added.

 A buffer has its greatest buffering capacity in the pH

range near its pKa (the negative log of its Ka).

 Two factors determine the effectiveness of a buffer:

 its pKa relative to the pH of the solution and
E.g. If you add a small amount of acid
 its concentration. (lowering pH) or base (raising pH), the buffer
will try to neutralize the change and
maintain the solution's pH within the 3.7-5.7
 The Henderson–Hasselbalch
Equation

 Defines the relationship between pH and concentrations of

un-dissociated acid and its conjugate base.
 A change in concentration of any component in an equilibrium
reaction necessitates a concomitant change in every
component.

 For example, an increase in [H+]


will decrease the concentration of conjugate base (e.g., lactate
ion)
 with an equivalent increase in the un-dissociated acid (e.g., lactic
acid).

 This relationship is conveniently expressed by


rearranging the equilibrium equation and

solving for H + , as shown for the following dissociation:
 Henderson-Hasselbach
Equation
HA = weak acid
1) Ka = [H ][A ]
+ -

[HA] A- = Conjugate base

2) [H+] = Ka [HA]
[A-]
3) -log[H+] = -log Ka -log [HA]
[A-]  H-H equation describes
the relationship between:
4) -log[H+] = -log Ka +log [A-]  pH,
[HA]  pKa and
 buffer
5) pH = pKa +log [A-] concentration

[HA]
 …
cont’d
 From this equation, you can see that a weak
acid is 50% dissociated at a pH equal to its
pKa.

 Most of the metabolic carboxylic acids have

pKa ‘s between 2 and 5, depending on the
other groups on the molecule.
 The pKa reflects the strength of an acid.

 Acids with a pKa of 2 are stronger acids than

those with a pKa of 5 because, at any pH, a
greater proportion is dissociated.
The body produces more acids than bases
 Acids are taken in with foods.
 Cellular metabolism produces CO2.
 Acids are produced by metabolism of
lipids and proteins. CO 2

Volatile acid H2CO3 CO2+ H2O CO2 CO2

H2SO4 H3PO4
Fixed acid Uric acid
Lactic acid
Ketone body
52
 …cont’d
• Acidic Substances of body:
– Carbonic acid(H2CO3)
– Phosphoric acid( H3PO4)
– Sulphuric acid (H2SO4)

• Organic Acids:
– Lactate, Acetoactate, Pyruvate

• Alkaline Substances of body:

– Citrate
– Bicarbonates.
 Maintenance of blood pH
 Three lines of defense to regulate
the body’s acid-base balance
 Blood buffers

 Respiratory mechanism

 Renal mechanism

55
 Buffer systems
 Take up H+ or release H+ as
conditions change
 Buffer pairs – un dissociated weak
acid and its conjugate base

 Exchange a strong acid or base for a

weak one
 Results in a much smaller pH change

56
Buffer Action: Resisting pH Changes
 1. Adding Acid:
 * When you add acid (H+) to the buffer, the conjugate base reacts with the H+ to form
the weak acid.
 * This reaction consumes the added H+, minimizing the pH drop.

 2. Adding Base:
 * When you add base (OH-) to the buffer, the weak acid reacts with the OH- to form water
and the conjugate base.
 * This reaction consumes the added OH-, minimizing the pH increase.

 Analogy: Like a Sponge

 Think of a buffer like a sponge:

 • The sponge: The weak acid and its conjugate base act like the sponge's material.

 • Absorbing acid/base: The sponge readily absorbs small amounts of acid or base (H+ or
OH-) without significantly changing its overall "wetness" (pH).
 Principal buffers in blood
in Plasma in RBC

H2CO3 / HCO3- 35% 18%

HHb / Hb- 35%

HPro / Pro- 7%

H2PO4- / HPO42- 5%
Total 42% 58%
58
 Bicarbonate buffer
 Predominant buffer system in ECF
 Sodium Bicarbonate (NaHCO3) and carbonic
acid (H2CO3)
 HCO3- : H2CO3: Maintain a 20:1 ratio

[HCO3 － ]
pH=pKa+Log
H2CO3 H+ + HCO3- [H2CO3]
24
= 6.1+ lg
1.2
20
= 6.1+ lg
1
= 6.1+1.3 = 7.4 59
 Bicarbonate buffer
 HCl + NaHCO3 ↔ H2CO3 + NaCl

 NaOH + H2CO3 ↔ NaHCO3 + H2O

 Action of Bicarbonate (NaHCO3):


converts strong dissociable acid into weak non
dissociable acid (H2CO3) and a neutral salt without
altering the pH.

 Weak acid H2CO3 formed during buffering action

of Bicarbonate buffer is then expired out by
Lungs. 60
 …cont’d

•Thus Bicarbonate buffer is connected to the respiratory

system.
– Bicarbonate buffer is also termed as Respiratory buffer.

•Alkali reserve is represented by the concentration of

NaHCO3 in the blood.

•Alkali reserve concentration(HCO3-) determines :

– the strength of buffering action towards added H+ ions by
acids.

•The more the concentration of Alkali reserve, the greater

is the buffering action and vice versa.
 Phosphate buffer
 Major intracellular buffer
 NaH2PO4-Na2HPO4

 H+ + HPO42- ↔ H2PO4-

 When H+ ions added they are

neutralized/fixed by Na2HPO4 (Alkaline
Phosphate) and converted to NaH2PO4 (Acid
Phosphates). 63
 …cont’d

 These acid phosphates then excreted out

through kidneys as acidic urine.

 Thus Phosphate Buffer is connected to Excretory system .

 Phosphate Buffer also termed as Urine Buffer.

OH- + H2PO4- ↔ H2O + HPO42-

 When an alkali enters it is buffered by the acid

phosphate NaH2PO4 which is converted to Na2HPO4
alkaline phosphate.
 Excreted in urine making it alkaline urine.
 Protein Buffers
 Include plasma proteins
and hemoglobin

 Carboxyl group gives up H+

 Amino Group accepts H+

65
Protein Buffer
Hemoglobin Buffer

67
2. Respiratory mechanisms
 Exhalation of CO2 CO2 CO2

 Rapid, powerful, but only works with

volatile acids
 H+ + HCO3- ↔ H2CO3 ↔ CO2 + H20

 Doesn’t affect fixed acids like lactic acid

 Body pH can be adjusted by changing

rate and depth of breathing
68
3. Kidney excretion
 Most effective regulator of pH
 The pH of urine is normally acidic (~6.0)

H+ ions generated in the body are eliminated by
acidified urine.

 Can eliminate large amounts of acid (→H+)

 Reabsorption of bicarbonate (HCO3-) (←HCO3-)
 Excretion of ammonium ions(NH4+) (→NH4+)
 2/3 of body acid load liberated in the form of NH 4+

 If kidneys fail, pH balance fails

69
Renal System maintains Acid
Base Balance through:

Reabsorption of Bicarbonate (HCO3-)
ions.

 Excretion of H+ ions

 Excretion of titrable acids(Acid

Phosphates)

 Excretion of Ammonium ions

(Glutaminase activity)
 Rates of correction
 Buffers function: almost
instantaneously

 Respiratory mechanisms: take several

minutes to hours

 Renal mechanisms: may take several

hours to days
71
72
73
 Non covalent bonds in biological
structures
• Non-covalent interactions are weak electrical bonds
between molecules.
• Types of non-covalent interactions are:
– ionic (electrostatic) bonds,
– H-bonds, and
– van der Waals interactions.
• Non-covalent interactions (1-5 kcal/mol) are typically
~100-fold weaker than covalent bonds .
– Easily broken but they are very important because
– they help to determine and stabilize the shapes of biological
molecules because they are "collectively strong."
 Ionic Interactions
 Ionic interactions occur between cations and anions.

Non-directional ionic bond interactions mean that

 These bonds are non-directional. the electrostatic attraction between positively and
negatively charged ions occurs in all directions. Unlike
covalent bonds, which are directional and form specific
angles between atoms, ionic bonds don't have a fixed
orientation.
 Bond strength depends on the medium (dielectric constant)
and it is less in polar than nonpolar solvents.

 Water is effective at screening the electrostatic interactions

between dissolved ions because :
it has a high dielectric constant, a physical property that
A high dielectric constant in a solvent
reflects the number of dipoles in a solvent. reflects both a large number of dipoles
and/or strongly polarized molecules,
allowing the solvent to shield charges
This means that the strength of an ionic bond can be affected by the solvent it's in. The dielectric
effectively and stabilize ions or polar
constant of a solvent is a measure of its ability to reduce the electrostatic force between ions.
molecules.
•Polar solvents like water have a high dielectric constant. This means they can effectively The number of dipoles refers to the
screen the charges of ions, weakening the ionic bond. total count of individual dipolar molecules
•Nonpolar solvents have a low dielectric constant, so they don't screen the charges as (having partial – and partial+ poles) within
effectively, resulting in stronger ionic bonds. a given sample or volume.
 …cont’d
Ionic compounds such as NaCl are readily dissolved in
water .

Water molecules:
hydrate and stabilize Na+ and Cl- ions,
weakening the electrostatic interactions between them and
countering their tendency to associate in a crystalline lattice.

The resulting increase in entropy (randomness) of the

system is largely responsible for the ease of dissolving
NaCl in water.
Solvation spheres of water
molecules surround ions in
solutions.
 Function of ionic bonds
They are important in all biological processes.

A few examples are:

 They play an important role in determining the shapes
(tertiary and quaternary structures) of proteins.
 They are involved in the process of enzyme catalysis.

 They are important in determining the shapes of

chromosomes.
 They play a role in muscle contraction and cell shape.

 They are important in establishing polarized membranes

for neuron function and muscle contraction.
 H-bonds
Hydrogen bonds result from
electrostatic attraction between electronegative atoms (such as
O or N) and
a hydrogen atom that is bonded covalently to a second
electronegative atom.
o Examples:
– N-H --- O=C -
– -O-H----- O=C -
These bonds represent the primary way in which :
water molecules interact with themselves and many types of
biomolecules .

Hydrogen bonds are weak bonds, typically about 3-5

kcal/mole.
Fig. Biologically important hydrogen bonds
 Importance of Hydrogen Bonds
• Source of unique properties of water

• Structure and function of proteins

• Structure and function of DNA

• Structure and function of polysaccharides

• Binding of substrates to enzymes

• Binding of hormones to receptors

• Matching of mRNA and tRNA

 Hydrogen Bond Directionality and Strength
 Hydrogen bonds are highly directional in that strength depends on
the proper alignment of the interacting atoms.
 The best alignment occurs when the orbital containing the
unshared electron pair of the acceptor atom is in line with the
covalent bond between the donor atom and H.
 Directionality confers bonding specificity as with the Watson-Crick
hydrogen bonds between the bases of double helical DNA (A-T; G-C), and
 results in very precise three dimensional structures for nucleic acid and
protein molecules.
 Van der Waals Interactions
 As any two atoms approach each other, electron clouds begin to
overlap.
Creates a situation known as "induced dipole".
 Van der Waals interactions are bonds between fluctuating,
induced dipoles within the electron clouds of interacting
molecules.

 These bonds can occur between nonpolar or polar molecules.

 Van der Waals bonds are extremely dependent on the distance

of separation between molecules and are significant only when
the electron clouds of the molecules are just touching.

 Van der Waals bonds are the weakest bonds:

1-2 kcal/mole.
 Biochemical significance of van der
Waals interactions
Weak Individually
 Easily broken, reversible.

Universal
 Occur between any two atoms that are near each other.

Importance
 Determines steric complementarity
 Stabilizes biological macromolecules (stacking in DNA)
 Facilitates binding of polarizable ligands
 The Hydrophobic Effect
• Refers to the association or folding of nonpolar
molecules in the aqueous solution.

• Is one of the main factors behind:

– protein folding
– protein-protein association
– formation of lipid micelles
– binding of steroid hormones to their receptors

• Does not arise because of some attractive direct force

between two nonpolar molecules.
 The Hydrophobic Effect
Refers to the entropy-driven aggregation of nonpolar
molecules in aqueous solution.

This is not an attractive force, but rather a

thermodynamically driven process.

The hydrophobic effect drives:

 the formation of membranes,
 contributes to the folding of proteins and
 the formation of double helical DNA.

 Fig. Next slide shows the cage-like structures formed by water

molecules surrounding a non-polar solute.
The Hydrophobic Effect
The Hydrophobic Effect
 References
 DM Vasudevan, Sreekumari S. Text Book of Biochemistry
for Medical Students, 7th Edition. Jaypee Brothers Medical
Publishers Ltd. New Delhi

 Murray R.K et al. Harper's illustrated Biochemistry 30th

edition .

 Pamela C.C, and Richard A.H., Lippincott's Illustrated

Reviews: Biochemistry 6th edition, J.B.

 Thomas M. Devlin. Text Book of Biochemistry with Clinical

Correlations. 7th Edition, Wiley-Liss Publication, USA

 Marks' Essential Medical Biochemistry, 4th Edition

Copyright Lippincott Williams & Wilkins.
,