1. Dr. Mamoun Ahram Nursing First semester, 2017
Enzymes-cofactors
Dr. Mamoun Ahram
Nursing
First semester, 2017

2. Resources The Medical Biochemistry Pages
Introduction to Vitamins and Minerals

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

4. Apoenzymes vs. holoenzymes

5. Vitamin derivatives as cofactors
Vitamins are organic molecules required in only trace amounts that must be obtained through the diet.
Vitamins are a dietary necessity for humans because our bodies do not have the ability to synthesize them.
Vitamins are grouped by solubility into two classes: water-soluble and fat-soluble.

6. Water-soluble vitamins

7. Fat-soluble vitamins

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

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

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

11. α-ketoglutarate dehydrogenase
Decarboxylation of α-ketoglutarate into succinyl CoA by α-ketoglutarate dehydrogenase

12. Riboflavin (vitamin B2)
The precursor for the coenzymes flavin adenine mononucleotide (FMD) and flavin adenine dinucleotide (FAD)
It is found in 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. Pyruvate dehydrogenase complex
NAD+ is a cosubstrate for the pyruvate dehydrogenase complex.

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)
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. Vitamin A
Vitamin A, which is essential for night vision, healthy eyes, and normal development of epithelial tissue, has three active forms: retinol, retinal, and retinoic acid.

30. Vitamin D Vitamin D is derived from cholesterol
It is synthesized when ultraviolet light from the sun strikes a cholesterol derivative in the skin.
It is transported into the liver where it is metabolized, then to the kidney, vitamin D is converted to the active hormone.
It regulates calcium absorption and bone formation.
Vitamin D deficiencies result when there is little exposure to sunlight.

31. Vitamin E The active form is called -tocopherol.
It is an antioxidant.
It prevents the oxidation of vitamin A and polyunsaturated fats.
Vitamin E apparently is not toxic in overdosage as are the other fat-soluble vitamins.

32. Vitamin K
This vitamin is essential to the synthesis of several blood-clotting factors.
It is produced by intestinal bacteria, so deficiencies are rare.

33. Antioxidants An antioxidant is a substance that prevents oxidation.
Our principal dietary antioxidants are vitamin C, vitamin E, -carotene, and the mineral selenium.
They remove the potentially harmful action of free radicals (highly reactive molecular fragments with unpaired electrons (for example, superoxide ion, ).
Free radicals become stable when they gain electrons from nearby molecules, which are thereby damaged.