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Enzymes-cofactors

Enzymes-cofactors. Dr. Mamoun Ahram. Resources. Biochemistry. 5th edition. Berg JM, Tymoczko JL, Stryer L. New York: W H Freeman; 2002. 8.1.1 Many Enzymes Require Cofactors for Activity http://www.ncbi.nlm.nih.gov/books/NBK22380/

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Enzymes-cofactors

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  1. Enzymes-cofactors Dr. Mamoun Ahram

  2. Resources • Biochemistry. 5th edition. Berg JM, Tymoczko JL, Stryer L. New York: W H Freeman; 2002. • 8.1.1 Many Enzymes Require Cofactors for Activity • http://www.ncbi.nlm.nih.gov/books/NBK22380/ • Section 9.2 Making a Fast Reaction Faster: Carbonic Anhydrases • http://www.ncbi.nlm.nih.gov/books/NBK22599/ • The Medical Biochemistry Pages • Introduction to Vitamins and Minerals • http://themedicalbiochemistrypage.org/vitamins.php

  3. Cofactors • What are cofactors? • What are coenzymes? • When are coenzymes called prosthetic groups and when are they cosubstrates?

  4. Classification of cofactors

  5. Apoenzymes vs. holoenzymes

  6. Vitamin derivatives as cofactors • What are vitamins? • Why are they important? • What are the two classes of vitamins?

  7. Vitamin C • Ascorbic acid • Example: prolyl hydroxylase • synthesizes 4-hydroxyproline (collagen) • An antioxidant

  8. Thiamin (vitamin B1) • Active form: thiamin pyrophosphate, TPP

  9. Pyruvate dehydrogenase complex • Decarboxylation of pyruvate into acetyl CoA by the pyruvate dehydrogenase complex

  10. α-ketoglutarate dehydrogenase • Decarboxylation of α-ketoglutarate into succinyl CoA by α-ketoglutarate dehydrogenase

  11. Riboflavin (vitamin B2) • The precursor for the coenzymes flavin adenine mononucleotide (FMD) and flavin adenine dinucleotide (FAD)

  12. Flavoproteins • Protiens that require FMN or FAD as cofactors • Redox reactions • FAD and FMN are prosthetic groups

  13. Succinate dehydrogenase • Oxidation of succinate into fumarate by succinate dehydrogenase

  14. Pyruvate dehydrogenase complex • FAD is a prosthetic group for the pyruvate dehydrogenase complex • It does not change in the overall reaction

  15. Niacin (vitamin B3) • Precursor of nicotinamide adenine dinucleotide (NAD+) and nicotinamide adenine dinucleotide phosphate (NADP+) • Cofactors for numerous dehydrogenases • Cosubstrates

  16. Pantothenic acid (vitamin B5) • Precursor of alanine and pantoic acid • Synthesis of coenzyme A (CoA) • Metabolism of carbohydrate, fats and proteins

  17. Coenzyme A • Coenzyme A transports acetyl groups from one substrate to another • via reactive thioester bond

  18. Pyruvate dehydrogenase complex • Decarboxylation of pyruvate into acetyl CoA by the pyruvate dehydrogenase complex

  19. Citrate synthase • Condensation of acetyl CoA and oxaloacetate into citrate by citrate synthase

  20. Pyridoxal phosphate (vitamin B6) • Pyridoxal, pyridoxamine and pyridoxine are precursors of active form • Metabolism of amino acids

  21. Aminotransferases • All aminotransferases contain the prosthetic group pyridoxal phosphate (PLP)

  22. Examples • Aspartate aminotransferase • Alanine aminotransferase

  23. Biotin • Carboxylation reactions

  24. Pyruvate carboxylase • condensation of CO2 to pyruvate forming oxaloacetate by pyruvate carboxylase

  25. Acetyl CoA carboxylase • Carboxylation of acetyl CoA to malonyl CoA by acetyl CoA carboxylase initiating fatty acid synthesis • Biotin is a prosthetic group

  26. Cobalamin (vitamin B12) • Composed of a tetrapyrrol ring structure and a cobalt ion in the center • Two significant reactions • linking fatty acid metabolism to sugar metabolism by rearranging methylmalonyl CoA to succinyl CoA • the formation of methionine from homocysteine by methylation

  27. Folic acid • Reduced within cells to tetrahydrofolate (THF) by dihydrofolate reductase (DHFR), an NADPH-requiring enzyme • THF derivatives carry and transfer of one carbon units during biosynthetic reactions, especially of nucleotides

  28. Lipoic acid • Not a dietary requirement in humans • Not a vitamin • A co-factor in pyruvate dehydrogenase and α-ketoglutarate dehydrogenase

  29. Metals

  30. Example

  31. الله معاكموكل عام وأنتم بخير

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