1. Enzymes-cofactors
Dr. Mamoun Ahram

2. Resources The Medical Biochemistry Pages
Biochemistry. 5th edition. Berg JM, Tymoczko JL, Stryer L. New York: W H Freeman; 2002.
8.1.1 Many Enzymes Require Cofactors for Activity
Section 9.2 Making a Fast Reaction Faster: Carbonic Anhydrases
The Medical Biochemistry Pages
Introduction to Vitamins and Minerals

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

4. Classification of cofactors
Metals
Metallo-proteins
Metal-associated proteins
Small organic molecules
Coenzymes
cosubstrates

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

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

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

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

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

21. Pyridoxal phosphate (vitamin B6)
Pyridoxal, pyridoxamine and pyridoxine are precursors of active form
Metabolism of amino acids
pyridoxal phosphate
Pyridoxamine
Pyridoxal
Pyridoxine

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

23. Examples
Aspartate aminotransferase
Alanine aminotransferase

24. Biotin
Carboxylation reactions

25. Pyruvate carboxylase
condensation of CO2 to pyruvate forming oxaloacetate by pyruvate carboxylase

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

27. 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

28. 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

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

30. Glutathione peroxidase
Metals
Enzyme
Metal
Carbonic anhydrase
Zn2+
Carboxypeptidase
Hexokinase
Mg2+
Glutathione peroxidase Se
Superoxide dismutase
Mn2+

31. Example

36. الله معاكم وكل عام وأنتم بخير