Chapter 1: Biochemistry: An Evolving Science 2nd August 2012

Biochemical Unity And Diversity

Biodiversity
What does Bio mean?

Bio =
2

Biodiversity
What does Diversity mean?

Diversity = Variety
3

Sea Urchins
Plant (Indian poke)

Common House Cat

diversity determined by DNA sequence

have distinct morphologies Biochemical commonality that attests to a common ancestry

4
http://www.ncbi.nlm.nih.gov/books/NBK22462/figure/A154/?report=objectonly

Diversity of Life - Evolution and Mutation

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

At biochemical level, many organisms have common features CELLS: Construction of animals, plants and microorganisms from cells suggested That these diverse organisms have much more in common.

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.

Biochemistry is study of chemistry of life processes.

All things are made up of the same units of matter: atoms, molecules Interplay of two different classes of molecules: Large biological macromolecules eg proteins & Nucleic acids (DNA; RNA) & Small low-molecular weight molecules metabolites (glucose & glycerol)

Chemical transformations that converts Glucose and O2 into CO2 and water is identical in bacteria and human beings. ..indicate a commonality
7
http://www.accessexcellence.org/RC/VL/GG/structure.php

Perhaps All Disease Has a Biochemical Basis

1. Physical agents:

Mechanical trauma, extremes of temperature, sudden changes in atmospheric pressure, electric shock. 2. Chemical agents Certain toxic compounds, therapeutic drugs, etc. 3. Biologic agents Viruses, bacteria, fungi, higher forms of parasites. 4. Oxygen lack Loss of blood supply, depletion of the oxygen-carrying capacity of the blood, poisoning of the oxidative enzymes. 5. Genetic disorders Congenital, molecular. 6. Immunologic reactions Anaphylaxis, autoimmune disease. 7. Nutritional imbalances Deficiencies, excesses. 8. Endocrine imbalances Hormonal deficiencies, excesses.
8

Harpers Biochemistry book

More Common Traits

Use of energy (eg Photosynthesis) Stimuli Sense and response Cells Unicell to Multi-cell Universal genetic code (DNA) Reproduction Growth and development Adapt and change over time

Proteins, the macromolecules are key participants in most biological processes

9
Image source: http://www.scq.ubc.ca/a-monks-flourishinggarden-the-basics-of-molecular-biology-explained/

Three Domains on this basis of biochemical characteristics

Sources of Change Mutation Natural Selection Artificial Selection

TREE OF LIFE Eukarya Prokarya Archaea multicellular organisms (nucleated) human beings Unicellular Organisms (no nucleus) 10 bacteria (early in evolution) have some distinguishing features

DNA illustrates the interplay between Form and Function

1953 Watson-Crick

Use of DNA for storage of genetic information. Linear Polymer made up of four different monomers

Fixed backbone built of sugar-phosphate units. Sugars are deoxyribose ; Bases are planar

11

Each Sugar is connected to two phosphate groups

DNA

Oriented in same way so each DNA strand is polar with one end distinguishable from the other.

Phosphodiester bridges

Bases are connected to the sugar components

12

Two Single Strands of DNA combine to form a double helix

Double helix composed of two intertwined strands sugar-phosphate backbone lies on the outsdie and the bases on the inside

Bases form specific base-pairs held together by H-Bonds

13

Watson-Crick base pairs

Adenine pairs with Thymine: 2 H-bonds

Guanine pairs with Cytosine: 3H Bonds

H-Bonds are much weaker than covalent bonds Why are these weak bonds crucial in biochemical systems?

14 *non-Watson Crick basepairs are also known; mispairs/wobble basepairs, hoogsteen basepairs etc

DNA Structure explains Heredity and the Storage of Information

Compatible with any sequence of bases Base pairs have essentially same shape and fit equally well into the center of the double helical structure of any sequence. Sequence of bases determines the genetic information DNA sequence determines the sequence of RNA (Ribonucleic Acid) and Protein Molecules

15

DNA Replication
Base-pairing dictates sequence of complementary strands
Because of base-pairing, sequence of bases along one strand completely determines the sequence along the other strand.

Possible Copying Mechanism

16

Concepts from Chemistry To explain the properties of Biological Molecules

17

Formation of DNA
Double helix can form from its component strands

Nearly to completion: if there is equal concentration of DNA at 25C in presence of [NaCl] What causes the two strands of DNA to bind together?
18

https://www.youtube.com/watch?v=0qoqzErrae4

Covalent and Non-Covalent bonds are important for structure and Stability of Biological Molecules COVALENT BONDS

Strongest and high energy is needed to break them Bond length: 1.54 Bond Energy: 356 kJ mol-1 Formed by sharing a pair of electrons between adjacent atoms

Multiple covalent bond, more than one electron pair shared eg. (C=O) double bond: common in DNA Covalent bonds can be represented through resonance structures
19

Benzene: Two forms

Composite of resonance structures with increased stability ADENINE True structure is a composite of both the structures

The observed bond length (1.40 ) is between C-C (1.54 ) and C=C (1.34 )

20

Reversible Interactions: Noncovalent Bonds

Weaker but crucial for biochemical processes such as formation of double helix

Four Types Electrostatic Hydrogen bonding van der Waals interactions and Hydrophobic interactions
21

Differ in geometry, strength and specificity

Non-Covalent Bonds: Reversible Interactions:

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

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 3 in water has Ions separated by 3 in hexane has
(dielectric constant of 2)

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

22

Hydrogen bonds
Fundamentally Electrostatic Needed for specific base-pairs (eg in DNA) Shared between two electronegative atoms Weaker than covalent bonds 4- 20kJ mol-1 (1-5 kcal mol-1) Longer than covalent bonds upto 2.6

Tightly linked

Weakly linked

H-bonds are biochemically important as they can easily be broken but strong enough 23 to stabilize double helix .

van der Waals Interactions van der Waals interaction is the sum of the attractive or repulsive forces between molecules other than those due to covalent bonds, the hydrogen bonds, or the electrostatic interaction arises due to asymmetric charge distribution around atoms induces a complementary asymmetric charge for nearby atoms leading to attraction 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) However, when two large molecules come together, the net effect can be substantial

24

Water: Effect on Biomolecular Interactions

Majority of biological interactions take place in H2O

Important properties of H2O:

H2O is a polar molecule Charge is asymmetric (molecule is bent) O2 draws electrons away from two H-Nuclei Leaving the region with net positive charge.

H2O is highly cohesive H-bond interaction highly polar nature is responsible for high dielectric constant (80)

25

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

aggregation of nonpolar groups leads to release of water molecules The release of water molecules into solution makes the aggregation of nonpolar groups favorable and tend to associate with one another in water. This tendency is called hydrophobic effect
26

The double helix is an expression of Rules of Chemistry

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?
27

Double Helix is an expression of the Rules of Chemistry Electrostatic interactions negatively charged phosphate oppose formation of double helix but ionic species such as Na+/ Mg2+ neutralize the repulsions

H-Bonds DNA base pairs are formed via H-Bonds (two bases that are non-complementary??) In single stranded DNA, bases H-bond with H2O in solution and they tend to be broken when duplex is getting formed

28
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 3.4 separates the planes and 3.6 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

29