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

Resources The Medical Biochemistry Pages Introduction to Vitamins and Minerals http://themedicalbiochemistrypage.org/vitamins.php

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

Apoenzymes vs. holoenzymes

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.

Water-soluble vitamins

Fat-soluble 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) It is found in 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

Pyruvate dehydrogenase complex NAD+ is a cosubstrate for the pyruvate dehydrogenase complex.

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 pyridoxal phosphate Pyridoxamine Pyridoxal Pyridoxine

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

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.

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.

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.

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

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.