Details of ID4101 (Autumn 2012)

Level: 4 Type: Theory Credits: 3.0

Course CodeCourse NameInstructor(s)
ID4101 Chemical Perspectives of Biological Pathways Subhajit Bandyopadhyay

Syllabus
ID4101: Chemical perspectives of biological pathways



The foundations : The course will start with some of the basic topics in chemistry.



Acidity, basicity, the importance of understanding of pKa in biosystems .



Thermodynamics in biological systems Open systemsnon-equilibrium conditions; coupled systems .

Amino acids (recap.) Enzymes : Proximity effects Orientation of the substrates, Rate acceleration, Enzyme kinetics (recap.); Pre-steady state kinetics (stop-flow methods), inhibition modes kinetic analysis and inhibition mechanisms (foundations of basic drug design based on inhibitors); Catalysis: Covalent catalysis, non-covalent catalysis, catalyst in electrostatic binding mode, general acid-general base catalysis, specific acid/base catalysis.



Chemical selectivity in biology through Molecular recognition. Role of chirality, specific examples: including glycobiology design of vaccines (HIV, ovarian cancer) .



Mechanisms principles of arrow pushing (recapitulation of dos and donts) Reactions found in biological systems. The roles of the enzymes, coenzymes/cofactors in the transformation in the following reaction pathways. Roles of metal ions.



Classification of enzymes according to their functions. One enzyme one function? Catalytic promiscuity of enzymes selection pressure development of new functions. Basic protein engineering.



Classification: Oxidoreductases; Transferases; Hydrolases; Lyases; Isomerases; Ligases or Synthetases (definition: examples; details of these classes will be discussed later)



Principal pathways (mainly catabolic pathways) Carboxylation/decarboxylation; Condensation reactions; Fatty acid chain extension; Isoprene condensation reactions; Carbocation rearrangements (in biosynthesis); Transamination; Tyrosine and tryptophan as precursors; Oxidative phenolic coupling



Antibody catalyzed reactions Artificial enzymes, molecular recognition with antibodies, transition state analogs for eliciting antibodies, chemically difficult reactions catalyzed by antibodies. Prodrug activation by antibodies and reduction of side effects.



Oxidation/phosphorylation

Biological redox reactions nicotinamide and flavin dependent coenzymes (general structure activity difference between the two coenzymes examples: alcohol dehydrogenase, [review of prochirality] monoamine oxidase, UDP-galactose 4-epimerase, dihydropyrimidine dehydrogenase, D-aminoacid oxidase. Regeneration of reduced coenzymes (NADPH/FADH2) by dioxynen.



DNA damage and repair mechanism (base excision mechanism)



Metabolic pathways: Lipid metabolism; Carbohydrate metabolism; Amino acid metabolism; Nucleic acid metabolism .



Biosynthesis of some natural products

Antibiotics: Penicillin, erythromycin & combinatorial biosynthesis for synthesis of new polyketides



Fatty acids

Terpenoid classification and biosynthesis



Prostaglandins, Cyclooxygenase enzymes (COX 1 and COX 2), biosynthesis via arachidonic acid pathway, COX inhibitor design: need for COX 2 selectivity, the VIOXX blunder.



Alkaloids: (This lecture is preceded by a lecture of arginine catabolism, putrescine biosynthesis, and related topic arginase activity structure, arginase, NO synthase and sexuality) Cocoaine, nicotine, and atropin from putrescine.



NRPS (non ribosomal peptide synthase)



Tetrapyrroles: Vitamin B12, heme, bilirubin etc.



Prerequisite: 2nd year level Organic chemistry.





References
Suggested Text/Reference Books :



1. Biochemistry, Geoffrey Zubay, William C Brown Pub; 4th edition, 1999.

2. Biochemistry, 3rd Edition, Donald Voet and Judith Voet, Wiley, 2004.

3. Biochemistry, 5th Edition, Jeremy M Berg,1 John L Tymoczko,2 and Lubert Stryer, W. H. Freeman and Company, 2002

4. Enzyme Structure and Mechanism, 2nd Edition, Alan Fersht, W H Freeman, New York. 1984



Course Credit Options

Sl. No.ProgrammeSemester NoCourse Choice
1 IP 1 Not Allowed
2 IP 3 Not Allowed
3 MS 7 Core
4 RS 1 Not Allowed