BIOL 158: BIOLOGICAL CHEMISTRY II

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1 BIOL 158: BIOLOGICAL CHEMISTRY II Lecture 5: Vitamins and Coenzymes Lecturer: Christopher Larbie, PhD

2 Introduction Cofactors bind to the active site and assist in the reaction mechanism Apoenzyme is an enzyme lacking its cofactor Holoenzyme is an enzyme with its cofactor

3 Classification of Cofactors

4 Inorganic Cation Cofactors The metal ion is tightly bound and participates in the catalytic mechanism more directly Or metal ions participate directly in electron transfers during oxidation-reduction reactions Metal Ion Fe 2+ of Fe 3+ Cu 2+ Zn 2+ Mg 2+ Mn 2+ Enzyme Cytochrome oxidase, Catalase, Peroxidase Cytochrome oxidase DNA polymerase, Carbonic anhydrase, Alcohol degydrogenase Hexokinase, Glucose-6-phosphatase Arginase K + Pyruvate kinase (also requires Mg 2+ ) Ni 2+ Mo Se Urease Nitrate reductase Glutathione peroxidase

5 Vitamins Vitamins are compounds that are required in the diet, because the organism cannot synthesize them, or the rate of usage by the organism typically exceeds the rate of synthesis of the compound.

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7 Vitamin B3 (niacin) NAD/NADP Coenzyme

8 NAD and NADP act as soluble electron carriers between proteins. Substrates for enzymes involved in oxidation and reduction reactions. NAD (NADH) is primarily involved in catabolic reactions. NADPH (the reduced form of NADP) is primarily involved in biosynthetic reactions In most cells, NAD levels are much higher than NADH levels, while NADPH levels are much higher than those of NADP.

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10 Alcohol dehydrogenase an example of role of NAD in redox chemistry

11 Vitamin B2 - Riboflavin Riboflavin is the precursor to the flavin coenzymes FMN and FAD. Flavins are yellow in colour and are light sensitive Riboflavin deficiency is so rare that it has no name

12 FMN and FAD are non-covalently attached to their enzymes, but generally do not dissociate (prosthetic groups) They act as storage locations for electrons within proteins. The functional part is the isoalloxazine ring and can accept or transfer electrons one at a time, although they can carry up to two electrons.

13 Examples of Enzymes using FMN (a) Lactate dehydrogenase (pyruvate lactate) (b) Lactate 2-monooxygenase ((S)-lactate + O 2 acetate + CO 2 + H 2 O) Example of Enzymes using FAD (a) Malate oxidase ((S)-malate + O 2 oxaloacetate + H 2 O 2 ) (b) Glucose oxidase (glucose + O 2 D-glucono-δ-lactone + H 2 O 2 ) (c) Alcohol oxidase (a primary alcohol + O 2 an aldehyde + H 2 O 2 )

14 Vitamin C (ascorbic acid) Vitamin C acts as a reducing agent It is important in maintaining some metal cofactors in reduced state It is required for hydroxyproline and lysine hydroxylation (in collagen synthesis) by maintain the enzyme (prolyl hydroxylase) in the active form For dopamine β-hydroxylase activity (an enzyme essential for norepinephrine and epinephrine synthesis) For bile acid synthesis For tyrosine degradation Assists in iron absorption Is a general antioxidant

15 Maintaining some metal cofactors in reduced state..

16 A general antioxidant..

17 Vit C is important for Hydroxyproline synthesis which stabilizes the collagen triple helix by forming interstrand hydrogen bonds

18 Vitamin B12 - Cobalamin It is a methyl group carrier and for shifting hydrogen between two carbon atoms

19 Biochemical Role.

20 Cabalamin transport and deficiency (pernicious anaemia)

21 Folic Acid (Vit B9, Bc, M)

22 THF as a single carbon carrier

23 Functions of THF (Single carbon carrier )

24 Biotin (Vit B7, H or Coenzyme R) Active in carboxylase enzymes for the transfer of single carbon unit as CO 2

25 Biotin Cycle and functions

26 Biotin deficiency and raw egg consumption

27 Vitamin B1 Thiamin Thiamin is converted to the coenzyme thiamin pyrophosphate in an ATP-dependent reaction. Thiamin pyrophosphate is a coenzyme required for certain types of oxidative decarboxylation reactions, including the reactions catalyzed by the pyruvate dehydrogenase complex Deficiency in thiamin causes beriberi

28 Lipoic Acid or Alpha Lipoic Acid (ALA) Lipoic acid forms an amide link to a specific lysine residue of certain enzymes. The lipoamide prosthetic group acts as an acyl carrier.

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30 Vitamin B5 Pantothenic acid Pantothenic acid is the precursor of Coenzyme A and of the prosthetic group of the Acyl Carrier Protein domain in fatty acid synthase. The active form of the cofactor is produced by formation of a peptide bond to cysteine followed by decarboxylation of the cysteine residue, and then by conjugation to the remainder of the coenzyme

31 Central Role of CoASH

32 Vitamin B6

33 Pyridoxal phosphate is a prosthetic group by forming Schiff base with Lys ε-amino group

34 Aminotrasferase reactions (AST, ALT)

35 FAT SOLUBLE VITAMINS

36 Vitamin K

37 Vit K dependent carboxylase activity

38 Vitamin A Retinol acts as the precursor of the visual pigment 11-cis-retinal.

39 Retinol can be converted (irreversibly) to retinoic acid. All trans-retinoic acid and 9-cis-retinoic acid are ligands for nuclear receptors. Retinoic acid may have a role in glycoprotein biosynthesis Β-carotene and retinoids act as antioxidants

40 Vitamin D Can be synthesized from cholesterol (but requires sunlight) or provided in the diet

41 Vitamin E

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43 Summary of Antioxidant Activities of the cell