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?
Classification of cofactors
Apoenzymes vs. holoenzymes
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
PyridoxinePyridoxalPyridoxaminepyridoxal phosphate
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
Metals
MetalEnzyme
Zn2+ Carbonic anhydrase
Zn2+ Carboxypeptidase
Mg2+ Hexokinase
SeGlutathione peroxidase
Mn2+ Superoxide dismutase
Example
الله معاكموكل عام وأنتم
بخير
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