Chapter 1:

Biochemistry: An Evolving Science

3rd January 2011

TOPICS FOR SEMINAR

Cloning & Human cloning

Biometrics
NanoTechnology in medicine/ Nanomedicine
Astrobiology (http://en.wikipedia.org/wiki/Astrobiology)
DNA Computers/ Biocomputers
Stem Cells: A cure or disease?
Parkinsons Disease/ Alzheimers Disease/ Autism/ Dyslexia/
Drug Delivery Systems: A nanotechnology perspective
Bioterrorism /Bioweapons/ Defending Against Biological attack: Importance
Biodiesel/ Bio fuels
Molecular wires
GM crops
Diagnostic Imaging (Medical Contrast Agents) (e.g Optical Imaging/ MRI/ X-ray)
Invitro Fertilization
Genetic disorders (eg.Thalassemia)

BIOCHEMICAL UNITY AND DIVERSITY

Biodiversity
What does Bio mean?
Life

Bio =

Biodiversity
What does Diversity mean?

Diversity = Variety

Sea Urchins

Plant (Indian poke)

Common House Cat

diversity determined by DNA sequence
These have distinct morphologies
But Biochemically they display a remarkable
commonality that attests to a common
ancestry
6
http://www.ncbi.nlm.nih.gov/books/NBK22462/figure/A154/?report=objectonly

Biochemistry is study of chemistry of life processes.

Large Organisms have evolved from CELLS

The shape of a key molecule in

gene regulation (the TATA
binding protein) is similar in
three different organisms
separated by billion years of
evolution.

Chemical transformations that converts Glucose and O2 into CO2 and water
is identical in bacteria and human beings.

Lifes Levels of Organization

Subatomic particle
Atom
Molecule
Organelle
Cell
Tissue
Organ

Organ systems
Multicelled organism
Population
Community
Ecosystem
Biosphere

Source:
orgs.unca.edu/tulula/images/biodive
rsity.jpg

Pictures from websources (references due)

All things are made up of the same units of

matter: atoms, molecules

Unity of Life Characteristics of

Living Organisms

Use energy
(eg Photosynthesis)
Sense and respond to stimuli
Maintain homeostasis
The ability or tendency of an organism or cell to
maintain internal equilibrium by adjusting its
physiological processes

Made of cells
unicell to multi-cell

Universal genetic code

(DNA)
Reproduce
Grow and develop
Adapt and change over time
Proteins, the macromolecules are key participants in most biological processes
Image source: http://www.scq.ubc.ca/a-monks-flourishinggarden-the-basics-of-molecular-biology-explained/

Diversity of Life - Evolution and

Mutation

These changes may be:

Harmful: Hemophilia A
Beneficial: change in moth color during the industrial
revolution (adaptive trait)
Benign: 6 fingers or toes

The diverse organisms of modern world can be divided to three domains

Sources of Change
Mutation
Natural Selection
Artificial Selection

TREE OF LIFE
Eukarya
multicellular organisms (nucleated) human beings
ProkaryaUnicellular Organisms (no nucleus)
Archaea
bacteria (early in evolution) have some distinguishing features

DNA
A fundamental feature common to all cellular organisms is the use of DNA for
storage of genetic information.
Linear polymer made of four different monomers
Fixed backbone built of sugar-phosphate backbone.
Sugar is deoxyribose; hence the name.
Bases are planar
One end is distinguishable from other.

DNA

One of four bases attached to sugar, in any order

Sequence of bases constitutes the genetic information
Bases attached by Phosphodiester bridges

Bases are connected to the sugar components in DNA backbone

DNA

Watson-Crick double stranded DNA:

The Double Helix, 1953
Combination of two single strands
Sugar-phosphate backbone outside, bases inside
base pairs, held together by hydrogen bonds

Watson-Crick base pairs

A pairs with T

G pairs with C

Specific pairing means a way for possible copying mechanism for the genetic material
This base pairing along one strand determines the sequence along the other strand

Hydrogen bonds are weaker than covalent bonds (eg. C-C or C-N) and these are
biochemically important as they can easily be broken but strong enough to stabilize
double helix
*non-Watson Crick basepairs are also known; mispairs/wobble basepairs, hoogsteen basepairs etc

DNA Replication
Base-pairing dictates sequence of complementary strands
Each strand act as a template for the generation of its partner
strand

DNA Structure

Base pairs have same overall size and shape,

Fit neatly within double helix.
DNA structure compatible with any sequence of bases and can act as
efficient means of storing information.
Explains heredity and the storage of genetic Information.

Formation of DNA
Two complementary strands mixed together, they spontaneously
assemble to form a double helix

What causes the two strands of DNA to bind together?

Chemical bonds in biochemistry

To understand this chemistry/ binding within living systems, we should know
types of interactions & bonds in biochemical systems
and its/their energetic favorability

COVALENT BONDS
Formed by sharing a pair of electrons between adjacent atoms
strongest of all.
A C-C covalent bond has, bond length = 1.54, bond energy = 85
kcalmol-1
Very strong and high energy is needed to break them
Multiple covalent bond, more than one electron pair shared eg. (C=O)
double bond energies near 175 kcal mol-1

Benzene: Two forms

Composite of resonance structures with increased stability

ADENINE

True structure is a composite of both the structures

The observed bond length is between C-C and C=C

Reversible Interactions: Noncovalent Bonds

Weaker but crucial for biochemical processes

Four kinds,
electrostatic;
H-bonding;
van der Waals interactions and
hydrophobic interactions

Reversible Interactions: Noncovalent Bonds

1. Electrostatic interactions:
A charged group on one molecule can attract an oppositely charged group
on another molecule.
E = kq1q2/Dr2

[Couloumbs Law]

E Energy k = proportionality constant. (1389 kJmol-1/ 332 kcalmol-1

D = dielectric constant (H2O = 80)
q1 & q2 = electronic charges,
r is the distance between two atoms
How important is dielectric medium?

Ions separated by 3A in water has

Ions separated by 3A in hexane has

-5.8kJ mol-1
-55kJ mol-1

Hydrogen bonds
Responsible for specific base-pair formation
(e.g in DNA)
Shared between two electronegative atoms
Weaker than covalent bonds
4- 20kJ mol-1 (1-5 kcal mol-1)
Longer than covalent bonds

Tightly linked

Weakly linked

van der Waals Interactions

arises due to asymmetric charge distribution around atoms

The attraction increases when two atoms come close to each other until
separated by a contact distance (van der Waals contact distance)
Very Weak and small energies (0.5 to 1 kcal mol-1)

Water: Effect on Biomolecular Interactions

Majority of biological interactions take place in H2O

Important properties of H2O:

1. H2O is a polar molecule
2. H2O is highly cohesive
H-bond interaction highly polar nature
is
Responsible for high dielectric
constant
(80)

Hydrophobic Effect
Is a manifestation of the properties of Water
non-polar molecules cannot participate in H-bonding or ionic interactions
these interactions not favorable

surface interaction with H2O

aggregation of nonpolar groups

leads to release of water molecules

The release of water molecules into solution makes the aggregation of nonpolar
groups favorable

Formation of DNA
Two complementary strands mixed together, they spontaneously
assemble to form a double helix

What causes the two strands of DNA to bind together?

Can we associate those interactions?

Double Helix is an expression of the Rules of Chemistry

Electrostatic interactions
DNA has negatively charged phosphate
Oppose formation of double helix
but ionic species such as Na+/ Mg2+
neutralize the repulsions and aid formation
H-Bonds
In double helix DNA base pairs are formed via H-Bonds
In single stranded DNA, bases H-bond with H2O in solution
and they tend to be broken when duplex is getting formed
contribute to specificity not overall stabilization

https://www.msu.edu/course/isb/202/ebertmay/notes/snotes/02_15_07_
genes_evo2.html

van der Waals interactions

base pairs parallel & stacked on top of another
3.4A separates planes and 3.6 A separates
most closely approaching atoms (van der Waals distance)
Optimal in double helix.
Weak Stabilization

Hydrophobic Interactions

base stacking moves non-polar surfaces away from aqueous

media and decrease repulsion

True with any biomolecular assembly/interaction

Biochemistry, Entropy, & Laws of Thermodynamics

System: matter within a defined region of space
Surroundings: matter in the rest of the universe

1st Law: Total energy of a system and its surroundings is constant

Energy can neither be created or destroyed
Takes different forms:
Kinetic,
eg. Heat, random motion of molecules,
Potential
eg. Ball on top of a tower (develop KE as it falls)
related to a likelihood that atoms will react
eg. Oxygen and gasoline has a large PE because they may react to form CO2
and Water and release energy as heat
Energy released in the formation of chemical bonds must be used to break other
bonds, released heat or stored in some other form.

Some interconversions
between different forms of energy.
All energy forms are in principle,
interconvertible In all these
processes the total a mount of
energy is conserved

Entropy

From order to disorder:

Increasing Entropy
2nd Law: Total entropy of a system and its surroundings always increases for a
spontaneous process.
e.g. release of water from a non-polar surface is favorable as H2O molecules are
more disordered when they are free.

1 mole of O2

2 moles of H2

Uniform mixture Higher entropy

The general struggle for existence of animate beings is not a struggle for raw
materials these, for organisms, are air, water and soil, all abundantly available
nor for energy which exists in plenty in any body in the form of heat, but a struggle
for (negative) entropy, which becomes available through the transition of
energy from the hot sun to the cold earth : Ludwig Boltzmann
http://en.wikipedia.org/wiki/Entropy_and_life

Every system seeks to achieve a minimum of free energy

G = Hsystem - TSsystem
2nd Law: For a process to take place entropy of the Universe must increase,
& this will happen only if.
TSsystem > Hsystem
Entropy will increase if
G = Hsystem - TSsystem < 0

Free energy change must be negative for a process to occur spontaneously

http://en.wikipedia.org/wiki/Gibbs_free_energy

Thermodynamics in the formation of DNA

Single strands free to translate and rotate in

solution
Exists in more conformations than double helix
Thus, formation of double helix result in an
increase in order for the system.

DNA formation leads to loss of entropy

indicating that heat must be released to the
surroundings

Protein folding

High entropy

Free energy changes

Disordered
mixture

Spontaneous
process

Lower entropy

Folded
molecules

Genomic Revolution is Transforming Biochemistry and Medicine

Watson-Cricks suggestion that hereditary information is
stored as a sequences of bases along long strands of DNA
Human Genome Sequencing
identify all the approximately 20,000-25,000 genes in human DNA,
determine the sequences of the 3 billion chemical base pairs that
make up human DNA,
store this information in databases,
improve tools for data analysis,
transfer related technologies
address the ethical, legal, and social issues (ELSI)
Cultural:
various population comparison & human history
course of evolution
http://www.ornl.gov/sci/techresources/Human_Genome/project/about.shtml

http://en.wikipedia.org/wiki/Human_Genome_Project

Studies of human genome are revealing

disease origins and other biochemical
mysteries
Human Chromosomes contain the DNA
molecules that constitute human genome.
The staining pattern serves to identify specific
regions of chromosomes.

Gene in this region encodes a protein

When malfunctioning causes cystic
fibrosis.

The ultimate goal of this initiative is to understand the human genome and
knowledge of the human as necessary to the continuing progress of medicine
and other health sciences.
discusses the progress and challenges of identifying
structural variation signatures in cancer genomes.

http://mkweb.bcgsc.ca/circos/guide/visual/

Many Human diseases are linked to variations of Human Genome Sequence

Sickle cell Anemia
Caused by a single base change of A to T

Human History
via comparative genomics of various organisms

Biochemistry & Human Biology

Biochemistry is an intrinsically beautiful & facinating body of
knowledge
We know the details of the most fundamental processes in
biochemistry, places a firm chemical foundation under other
biological sciences, has significant philosophical implications
Biochemistry is greatly influencing medicine & other fields
We know the molecular basis of many genetic and other
diseases.
Rational design of new drugs, New clinical diagnostics
Biochemical research is tackling some of the most exciting
questions in biology & medicine