Biochemistry LS2101 Slides PDF

BIOCHEMISTRY: LS2101 Dr. Partha P. Datta IISER Kolkata 1  Enzyme, vitamins and coenzymes Most Enzymes Are Proteins weak bonding between enzyme and substrate 2 3 4 5 ...

BIOCHEMISTRY: LS2101 Dr. Partha P. Datta IISER Kolkata 1  Enzyme, vitamins and coenzymes Most Enzymes Are Proteins weak bonding between enzyme and substrate 2 3 4 5  How Enzymes Work Enzymes Affect Reaction Rates, Not Equilibria 6 7 8 9 10 11 12 13 Acid-Base Catalysis Covalent Catalysis Metal Ion Catalysis 14 Enzyme Inhibitors 15 Types of Enzymes 16  Many Enzymes require cofactors for activity Apoenzyme + Cofactor = Holoenzyme Cofactors can be subdivided into two groups: (1) metals and (2) (2) small organic molecules called coenzymes A coenzyme or metal ion that is very tightly or even covalently bound to the enzyme protein is called a prosthetic group 17 18 19 Which Vitamins Are Coenzymes? All of the water-soluble vitamins and two of the fat-soluble vitamins, A and K, function as cofactors or coenzymes. Coenzymes participate in numerous biochemical reactions involving energy release or catabolism, as well as the accompanying anabolic reactions. In addition, vitamin cofactors are critical for processes involved in proper vision, blood coagulation, hormone production, and the integrity of collagen, a protein found in bones. 20 Water - Soluble Vitamins 1.Vitamin B1 - thiamine Converted to thiamine pyrophosphate coenzyme Acts by nucleophilic attack on C = O Permits C - C bond cleavage and formation 2.Vitamin B2 - riboflavin Incorperated in FMN (Flavin MonoNucleotide) and FAD (Flavin Adenine Dinucleotide) coenzymes Acts in Redox Reactions Can accept and donate 2 e- and 2 H+ 3.Vitamin B6 - pyridoxal (-ol, -amine) Converted to pyridoxal phosphate coenzyme Acts by forming Schiff base with -NH2 of substrate Permits cleavage of C - C, C - O, C - S, C - H, and C - N bonds in area of attachment Very versatile, but amino group needed in substrate 4.Vitamin B12 - cyanocobalamin Coordination complex of Co+ in a corrin ring Converted to 5'-deoxyadenosylcobalamin coenzyme Acts to exchange -H and another group on adjacent C's Transfers Methyl group from Me-THF to homocycteine to synthesize Met 21 Water - Soluble Vitamins 1.Nicotinamide (NIacin, nicotinic ACid vimintIN) Converted to NAD and NADP coenzymes Functions in Redox Reactions by accepting and donating 2e- and 1 H+ 2.Pantothenic Acid Converted to Phospho-form coenzyme Activates Acyl moieties for condensation and enolization 3.Biotin (vitamin H) Coenzyme Incorperates CO2 in B carboxylation reactions "Binds the egg white glycoprotein avidin with Kd = 10- 15 M Vitamins #5-7 are part of the B complex 4.Vitamin C - ascorbic acid ("antiscorbutic") ("anti-scurvy") involved in hydroxylation of proline in collagen, therefore important for wound healing Prevent common cold? How? 5.Folic Acid - pteroylglutamic acid Converted to tetrahydrofolic acid (THF) Carries C-1 groups at all oxidation levels More properly considered a substrate than a coenzyme 22 Lipid-Soluble Vitamins 1.Vitamin A - trans-retinol Converted to visual pigment cis-retinal (Also contributes to animal growth and development - How? Retinoic acid?) 2.Vitamin D - 7-dehydrocholesterol Converted to hormone 1,25-Dihydroxy vitamin D3 (Stimulates gene expression to regulate calcium metabolism) 3.Vitamin E - a-tocopherol Antioxidant Prevents sterility - in rats, How? 4.Vitamin K - phylloquinone in plants; menaquinone in aminals and bacteria Cofactor for formation of gamma-carboxyglutamic acid in serine proteases of blood clotting cascade, and some other Ca++ binding proteins. 23 Non-Vitamin Coenzyme 1.Lipoic Acid (Isolated in 1951 by Lester Reed at UT-Austin - he obtained 30mg from 10 tons of liver residue.) Relays electrons and acetyl groups between catalytic subunits of pyruvate dehydrogenase complex. 24 Figure. Selected examples of vitamins as coenzymes: (a) thiamin pyrophosphate; (b) flavin mononucleotide; (c) pyridoxal phosphate; (d) coenzyme A; and (e) methylcobalamin or coenzyme B12. Reproduced from Coenzymes, Encyclopaedia of Food Science, Food Technology and Nutrition, Macrae R, Robinson RK, and Sadler MJ (eds), 1993, Academic Press. 25