Details of ID4107 (Autumn 2018)

Level: 7 Type: Theory Credits: 4.0

Course CodeCourse NameInstructor(s)
ID4107 Chemical Perspectives of Biological Pathways Subhajit Bandyopadhyay

Syllabus
How does nature make, transform and manipulate biological molecules? What makes are these transformations extremely specific? How do these transformations occur at a tremendous rate? How can you inhibit certain physiological processes with inhibitors? Taking lessons from the nature, can we design enzyme like systems?
This course will focus on the fundamentals of chemical reactions in biological systems and more importantly, the chemical logic behind them. Emphasis will be given on writing reaction mechanisms and be complementary to other courses in chemistry.)
By the end of the course, you should be able to:
(i) address some of the most fundamental aspects of biology from simple chemical logic
(ii) to write mechanisms for common biological reactions
(iii) recognize common metabolites and their origin
(iv) to predict the biosynthesis of common types of natural products
Course Overview:
The foundation : The course will start with some of the basic topics in chemistry. The number of lectures with these basic topics will be decided after taking the pulse of the class.
Acidity, basicity, the importance of understanding of pKa in biosystems
Thermodynamics in biological systems Open systemsnon-equilibrium conditions; coupled systems: everything is connected!
Amino acids (recap.) Enzymes : Proximity effects Orientation of the substrates, Rate acceleration, Enzyme kinetics: Steady state and pre-steady state (stop-flow methods), derivation and detailed kinetic analysis of different inhibition modes; introduction to 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 (recap of chirality and pro-chirality). Why has nature chosen DNA to store information? Why did nature choose phosphate in the DNA backbone?Why does DNA have ribose and the bases?
Recap of organic reaction mechanisms principles of arrow pushing (recapitulation of dos and donts) Reactions found in biological systems. Importance 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; mechanism)
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 (covered under principal pathways); Amino acid metabolism; Nucleic acid metabolism
Biosynthesis of some natural products (one or two from each categories)
Alkaloids: Cocoaine, nicotine, and atropin from putrescine (This lecture is preceded by the lecture of arginine catabolism, putrescine biosynthesis, and related topic arginase activity structure arginase, NO synthase).
Antibiotics: Penicillin/erythromycin & combinatorial biosynthesis for synthesis of new polyketides. [Special topic: Antibiotic mechanism of action and resistance. Recent literature]
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.

References
References and handouts will be provided in the classroom. Lehningers Biochemistry is an useful source for the basic aspects.

Course Credit Options

Sl. No.ProgrammeSemester NoCourse Choice
1 IP 1 Not Allowed
2 IP 3 Elective
3 IP 5 Elective
4 MR 1 Not Allowed
5 MR 3 Not Allowed
6 MS 7 Elective
7 RS 1 Elective
8 RS 2 Elective