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

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