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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 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/ • 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
Cofactors • What are cofactors? • What are coenzymes? • When are coenzymes called prosthetic groups and when are they cosubstrates?
Vitamin derivatives as cofactors • What are vitamins? • Why are they important? • What are the two classes of vitamins?
Vitamin C • Ascorbic acid • Example: prolyl hydroxylase • synthesizes 4-hydroxyproline (collagen) • An antioxidant
Thiamin (vitamin B1) • Active form: thiamin pyrophosphate, TPP
Pyruvate dehydrogenase complex • Decarboxylation of pyruvate into acetyl CoA by the pyruvate dehydrogenase complex
α-ketoglutarate dehydrogenase • Decarboxylation of α-ketoglutarate into succinyl CoA by α-ketoglutarate dehydrogenase
Riboflavin (vitamin B2) • The precursor for the coenzymes flavin adenine mononucleotide (FMD) and flavin adenine dinucleotide (FAD)
Flavoproteins • Protiens that require FMN or FAD as cofactors • Redox reactions • FAD and FMN are prosthetic groups
Succinate dehydrogenase • Oxidation of succinate into fumarate by succinate dehydrogenase
Pyruvate dehydrogenase complex • FAD is a prosthetic group for the pyruvate dehydrogenase complex • It does not change in the overall reaction
Niacin (vitamin B3) • Precursor of nicotinamide adenine dinucleotide (NAD+) and nicotinamide adenine dinucleotide phosphate (NADP+) • Cofactors for numerous dehydrogenases • Cosubstrates
Pantothenic acid (vitamin B5) • Precursor of alanine and pantoic acid • Synthesis of coenzyme A (CoA) • Metabolism of carbohydrate, fats and proteins
Coenzyme A • Coenzyme A transports acetyl groups from one substrate to another • via reactive thioester bond
Pyruvate dehydrogenase complex • Decarboxylation of pyruvate into acetyl CoA by the pyruvate dehydrogenase complex
Citrate synthase • Condensation of acetyl CoA and oxaloacetate into citrate by citrate synthase
Pyridoxal phosphate (vitamin B6) • Pyridoxal, pyridoxamine and pyridoxine are precursors of active form • Metabolism of amino acids
Aminotransferases • All aminotransferases contain the prosthetic group pyridoxal phosphate (PLP)
Examples • Aspartate aminotransferase • Alanine aminotransferase
Biotin • Carboxylation reactions
Pyruvate carboxylase • condensation of CO2 to pyruvate forming oxaloacetate by pyruvate carboxylase
Acetyl CoA carboxylase • Carboxylation of acetyl CoA to malonyl CoA by acetyl CoA carboxylase initiating fatty acid synthesis • Biotin is a prosthetic group
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
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
Lipoic acid • Not a dietary requirement in humans • Not a vitamin • A co-factor in pyruvate dehydrogenase and α-ketoglutarate dehydrogenase