Dr. Maha I. Ahmad 1 Dr. Maha I. Ahmed Ref. Harper. 1)Define vitamins, classify them according to their solubility. 2)List the water-soluble ones. 3)Describe the role of water-soluble vitamins in metabolism giving three examples. 4)Define coenzymes, classify them according to their functions & describe their role in enzyme action.

Dr. Maha I. Ahmad 2 VVitamins are organic compounds that function in a wide variety of capacities within the body. TThey act as cofactors in various enzymatic reactions. TThey generally cannot be synthesized by mammalian cells, therefore must be supplied in diet. TThey are essential for normal growth and deficiency results in characteristic deficiency diseases. TThey are classified according to their solubility in water or fat solvents: I.Water soluble vitamins: Vitamin C and Vitamin B complex. II.Fat soluble vitamins: Vitamin A, D, E, K.

Dr. Maha I. Ahmad 3 Fat Soluble VitaminsWater Soluble Vitamins Insoluble. Insoluble. Soluble. Soluble. They need bile salts for digestion and absorption. They need bile salts for digestion and absorption. They need plasma carrier protein. They need plasma carrier protein. They can be stored in the body [liver]. They can be stored in the body [liver]. Rare. Rare. Toxicity and hypervitaminosis are common. Toxicity and hypervitaminosis are common. Soluble. Soluble. Insoluble. Insoluble. They are simply absorbed. They are simply absorbed. They don’t need plasma carrier protein [except B12]. They don’t need plasma carrier protein [except B12]. They are not stored in the body [except B12]. They are not stored in the body [except B12]. Excreted once their conc. exceeds renal threshold. Excreted once their conc. exceeds renal threshold. Rare. Rare. 1.Solubility in H2O. 2.Solubility in fat. 3. Absorption. 4.Transport in plasma. 5.Storage.6.Excretion.7.Toxicity.

Dr. Maha I. Ahmad 4 Fat Soluble VitaminsWater Soluble Vitamins Vitamin A Vitamin D Vitamin E Vitamin K Thiamin (B1) Riboflavin (B2) Niacin (B3) Pantothenic Acid (B5) Pyridoxal, Pyridoxamine, Pyridoxine (B6) Biotin Cobalamin (B12) Folic Acid Ascorbic AcidAscorbic Acid [C]

Dr. Maha I. Ahmad 5 Coenzymes DDef: They are heat stable organic molecules derived from vitamins. TThey have small molecular weight compared to enzymes. TThey are essential for the activity of many enzymes. MMost of them are loosely attached to enzymes [weak bonds] and are released from the apoenzymes after completion of the reaction. FFunction: They act as group carriers during biochemical reactions. TThey could be classified according to the transferred groups into: I.H carriers: NAD, NADP, FAD, FMN. II.Groups other than H: CoA, PP, Biotin, Folic Acid, TPP.

Dr. Maha I. Ahmad 6 TPP is necessary as a cofactor for the pyruvate and a- ketoglutarate dehydrogenases. Transketolase of the pentose phosphate pathway. Thiamin [B1] Thiamin pyrophosphate

Dr. Maha I. Ahmad 7 Riboflavin is the precursor for the coenzymes, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). The enzymes that require FMN or FAD as cofactors are termed flavoproteins. They are cofactors for dehydrogenases: e.g. succinate dehydrogenase, Acyl CoA dehydrogenase. FAD [nitrogens 1 & 5 carry hydrogens in FADH2] Riboflavin [Vit. B2].

Dr. Maha I. Ahmad 8 Nicotinic AcidNicotinamide Vitamin B3 is the precursor for the coenzymes: Nicotinamide adenine dinucleotide (NAD + ) and nicotinamide adenine dinucleotide phosphate (NADP + ). Both NAD + and NADP + function as cofactors for numerous dehydrogenase, e.g; lactate and malate dehydrogenases, glucose 6-P dehydrogenase. Niacin (nicotinic acid and nicotinamide)/vit.B3: NAD + NADH P

Dr. Maha I. Ahmad 9 Pantothenic Acid Coenzyme A Pantothenic acid is formed from β -alanine and pantoic acid. Pantothenate is required for synthesis of coenzyme A. CoA and is a component of the acyl carrier protein (ACP) domain of fatty acid synthase, and it carries fatty acids. Pantothenate is, therefore, required for the metabolism of carbohydrate via the TCA cycle and all fats and proteins. Pantothenic acid [vit.B5]:

Dr. Maha I. Ahmad 10 PyridoxaminePyridoxalPyridoxine Vitamin B 6 Pyridoxal Phosphate Pyridoxal, pyridoxamine and pyridoxine are collectively known as vitamin B6. All three compounds are efficiently converted to the coenzyme pyridoxal phosphate [PP]. PP functions as a cofactor in enzymes involved in transamination reactions required for the synthesis and catabolism of the amino acids, also in A.A. decarboxylases. In glycogenolysis, as a cofactor for glycogen phosphorylase

Dr. Maha I. Ahmad 11 Biotin Biocytin is the cofactor required for enzymes that are involved in carboxylation reactions [CO2 fixation], e.g. acetyl-CoA carboxylase and pyruvate carboxylase. It is a Co-Carboxylase. Carboxylation reactions are important for CHO, Lipid and Protein metabolism. Biotin [Vit. H]: Biotin is the precursor for the coenzymes Biocytin.

Dr. Maha I. Ahmad 12 Vitamin B12 is composed of a complex tetrapyrrol ring structure (corrin ring) and a cobalt ion in the center. Vitamin B12 is synthesized exclusively by microorganisms and is found in the liver of animals bound to protein as the coenzymes: Methycobalamin or 5'-deoxyadenosylcobalamin. Cobalamin [vitamin B12]:

Dr. Maha I. Ahmad 13 The vitamin must be hydrolyzed from protein in order to be active. Hydrolysis occurs in the stomach by gastric acids or the intestines by trypsin digestion following consumption of animal meat. The vitamin is then bound by intrinsic factor, a protein secreted by parietal cells of the stomach, and carried to the ileum where it is absorbed. Following absorption the vitamin is transported to the liver in the blood bound to transcobalamin II. Cobamides are coenzymes for: I. Methyl malonyl CoA Mutase [Methyl malonyl to succinyl CoA]. II. Methionine synthase [Methylation of Homocysteine to methionine].

Dr. Maha I. Ahmad 14 Positions 5-8 carry 4-hydrogens in tetrahydrofolate (THF) Folic acid is a conjugated molecule consisting of a pteridine ring structure linked to para-aminobenzoic acid (PABA) that forms pteroic acid. Folic acid itself is then generated through the conjugation of glutamic acid residues to pteroic acid. Folic acid is obtained primarily from yeasts and leafy vegetables as well as animal liver. Folic Acid:

Dr. Maha I. Ahmad 15 FFolic acid is reduced to its active coenzyme tetrahydrofolate (THF also H4folate). TThe function of THF derivatives is to carry and transfer various forms of one carbon units during biosynthetic reactions. TThe one carbon units are either methyl, methylene, methenyl, formyl or formimino groups.

Dr. Maha I. Ahmad 16 FunctionCoenzymeVitamin Oxidative decarboxylation Cofactors for dehydrogenases. Fatty acid carrier [Acyl carrier]. Cofactors for aminotransferases & decarboxylases of Amino Acids. Carboxylation reactions [Co-Carboxylase]. Carboxylation reactions [Co-Carboxylase]. One carbon metabolism. One carbon carrier. TPP FMN & FAD NAD & NADP CoA Pyridoxal Phosphate [PP] BiocytinCobamidesH4F Thiamin (B1) Riboflavin (B2) Niacin (B3) Pantothenic Acid (B5) Pyridoxal, Pyridoxamine, Pyridoxine (B6) Biotin Cobalamin (B12) Folic Acid

Dr. Maha I. Ahmad 17