Introduction Vitamins are an organic chemical compound which the body requires in small amounts for the metabolism and to protect your health. Vitamins assist the body in functioning properly by helping in the formation of hormones, blood cells, nervous-system chemicals and genetic growth. An over dose can be harmful to your health.

The Body & Vitamins The body can only produce one vitamin naturally by itself. This is vitamin D. All other vitamins that the body requires to function properly have to be derived from the diet. Lack of vitamins can have a serious affect on your health and may end in metabolic and other dysfunctions.

Vitamin Groups Vitamins are divided up into two main groups which are fat- soluble vitamins and water- soluble vitamins. Fat-soluble vitamins are usually found in foods that contain fat. The body stores the fat soluble vitamins and because of this, people don’t usually need to make a special effort to include them in their diet.

Vitamin Groups Water soluble vitamins can’t be stored in the body for a long time and have to be replenished everyday. In some cases when it’s not possible to obtain these vitamins in a regular diet, they have to be acquired by other vitamin supplements.

Water-Soluble Vitamins Water soluble Readily excreted – expensive urine Can be lost from food by cooking/storage Typically work as part of enzymes in metabolism Relatively high absorption rate Severe deficiencies rare Vitamins – Niacin, Thiamine, Folic Acid, Riboflavin, B12, and C.

Thirteen complete Vitamins Water soluble Vitamins  Vitamin B1 (Thiamin)  Vitamin B2 (Riboflavin)  Vitamin B6 (pyridoxine)  Vitamin B12 (Cyanocobalamin)  Vitamin Biotin (Vitamin H)  Vitamin C (Ascorbic Acid)  Vitamin P (Bioflavonoids)  Niacin (Niacinamide) Fat-Soluble Vitamins  Vitamin A & Beta carotene  Vitamin D  Vitamin E  Vitamin F (unsaturated fatty acids)  Vitamin K (Menadione)

Vitamin K cycle

Thrombin Activation

The common pathway

Thiamine pyrophosphate (TPP) is a derivative of thiamine (vitamin B1). Nutritional deficiency of thiamine leads to the disease beriberi. It affects especially the brain, because TPP is required for CHO metabolism, and the brain depends on glucose metabolism for energy.

FAD (Flavin Adenine Dinucleotide is derived from the vitamin riboflavin. The dimethylisoalloxazine ring system undergoes oxidation/reduction. FAD is a prosthetic group, permanently part of E 3. Reaction: FAD + 2 e H +  FADH 2

Glossitis (Fig. 10-4) Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Dermatitis of Pellegra (Fig. 10-5) Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Lipoamide includes a dithiol that undergoes oxidation/ reduction.

The carboxyl at the end of lipoic acid's hydrocarbon chain forms an amide bond to the  - amino group of a lysine residue of E 2, yielding lipoamide. A long flexible arm, including hydrocarbon chains of lipoate and the lysine R-group, links each dithiol of lipoamide to one of two lipoate-binding domains of E 2.

The final electron acceptor is NAD +. In the overall reaction catalyzed by the Pyruvate Dehydrogenase complex, the acetic acid generated is transferred to coenzyme A.

Sequence of reactions catalyzed by Pyruvate Dehydrogenase complex: 1.The keto C of pyruvate reacts with the carbanion of TPP on E 1 to yield an addition compound. The electron-pulling (+) charged N of the thiazole ring promotes CO 2 loss. Hydroxyethyl-TPP remains. 2.The hydroxyethyl carbanion on TPP of E 1 reacts with the disulfide of lipoamide on E 2. What was the keto C of pyruvate is oxidized to a carboxylic acid, as the lipoamide disulfide is reduced to a dithiol. The acetate formed by oxidation of the hydroxyethyl is linked to one of the thiols of the reduced lipoamide as a thioester (~).

Sequence of reactions (continued) 3.Acetate is transferred from the thiol of lipoamide to the thiol of coenzyme A, yielding acetyl CoA. 4.The reduced lipoamide, swings over to the E 3 active site. Dihydrolipoamide is reoxidized to the disulfide, as 2 e H + are transferred to a disulfide on E 3 (disulfide interchange). 5.The dithiol on E 3 is reoxidized as 2 e H + are transferred to FAD. The resulting FADH 2 is reoxidized by electron transfer to NAD +, to yield NADH + H +.

Acetyl CoA, a product of the Pyruvate Dehydrogenase reaction, is a central compound in metabolism. The "high energy" thioester linkage makes it an excellent donor of the acetate moiety. View an animation of the Pyruvate Dehydrogenase reaction sequence.animation

Acetyl CoA functions as:  input to Krebs Cycle, where the acetate moiety is further degraded to CO 2.  donor of acetate for synthesis of fatty acids, ketone bodies, & cholesterol.

Biosynthesis of Amino Acids: Transaminations Amino Acid 1 +  -Keto Acid 2 Amino Acid 2 +  -Keto Acid 1 Glutamate +  - Ketoglutarate + Pyridoxal phosphate (PLP)- Dependent Aminotransferase

Transaminations: Role of PLP Tautomerization

Vitamin-Coenzymes in Amino Acid Metabolism Vitamin B-6 : pyridoxal phosphate –Enzymes that bind amino acids use PLP as coenzyme for binding Transaminases Amino acid decarboxylases Amino acid deaminases

Absorption of Vitamin B-12 (Fig ) Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Vitamin-Coenzymes in Amino Acid Metabolism Vitamin B-12 –Catabolism of BCAA Methyl-malonyl CoA mutase (25-9 &10)

Vitamin-Coenzymes in Amino Acid Metabolism Vitamin B-12 –Methionine synthesis/recycling Methionine as a methyl donor –Choline and creatine synthesis –Homocysteine is product –HCys -> Met requires B-12

Vitamin-Coenzymes in Amino Acid Metabolism Folacin: Tetrahydrofolate (THF) –Carrier of single carbons Donor & receptor Glycine and serine Tryptophan degradation Histidine degradation Purine and pyrimidine synthesis

Ascorbic Acid Structure (AscH 2 )

AscH 2 is a Di-acid At pH 7.4, 99.95% of vitamin C will be present as AscH - ; 0.05% as AscH 2 and 0.004% as Asc 2-. Thus, the antioxidant chemistry of vitamin C is the chemistry of AscH -.

Forms of Ascorbate

Ascorbate Falling Apart

AscH - is a Donor Antioxidant AscH - donates a hydrogen atom (H  or H + + e - ) to an oxidizing radical to produce the resonance-stabilized tricarbonyl ascorbate free radical. AscH  has a pK a of -0.86; thus, it is not protonated in biology and will be present as Asc  -.

Ascorbate, Summary Ascorbate is a versatile, water soluble, donor, antioxidant. Thermodynamically, it can be considered to be the terminal, small-molecule antioxidant.