Biochemistry Vitamins 1. Water soluble vitamins 2. Fat soluble vitamins

1. Biochemistry Vitamins 1. Water soluble vitamins 2. Fat soluble vitamins

2. Objectives: To recognize vitamins by name To understand their distribution in various food sources To understand their role in metabolism To understand the signs and symptoms of diseases resulting from deficiencies

3. Vitamins A group of organic nutrients required in small quantities for a variety of biochemical functions and which , generally , cannot be synthesized by body and must therefore be supplied in the diet.

4. Water soluble vitamins 1. B-complex vitamins a) B-vitamins in energy metabolism Thiamine (B1) Riboflavin (B2) Niacin (B3) Biotin Pantothenic acid b) B-vitamins in methyl group metabolism conversions Folic acid Cobalamin (B12) c) B-vitamins in metabolic conversions Pyridoxine (B6) Pyridoxal Pyridoxamine 2. Vitamin C

6. Champe and Harvey, p. 106

8. Thiamine Food sources and distribution: Whole grain, meats, legumes (peas, beans and lentils) Signs and symptoms of deficiency Beri-beri: severe deficiency Primarily in areas where polished rice is primary food source Symptoms include dry skin, irritability, disorderly thinking and progressive paralysis Wet beriberi-cardiovascular symptoms, cardiac failure Infants: onset can be rapid, resulting in tachycardia and death (look to nutritional status of mother) Wernicke-Korsakoff syndrome: Primarily associated with severe alcoholism. Symptoms include apathy, loss of memory Wandering eye movement Toxicities, contraindications, and other notes Only known use in treating deficiency Commonly given to alcoholics in ER(emergency room) Excess of any one B-vitamin can cause deficiency of others.

9. Rubin and Farber, Pathology - 2nd edition, p. 329

11. Riboflavin Food sources and distribution: Milk, cheese, meat, leafy vegetables, breads, cereals Signs and symptoms of deficiency Sore throat, glossitis, cheilosis (red lips) Anemia, neuropathy Toxicities, contraindications and other notes Only known use in treating deficiency Excess intake can cause yellow urine Excess can interfere with B1 & B6

12. Rubin and Farber, Pathology - 2nd edition, p. 331

14. niacin Food sources and distribution: Fish, meat, poultry, cereal, nuts Tryptophan in diet can serve as alternative source Signs and symptoms of deficiency Pellagra (pella agra: rough skin) 3D’s: dermatitis, diarrhea, dementia red, swollen tongue observed in chronic alcoholics symptoms reverse within 24H of administration Toxicities, contraindications and other notes Harnup’s disease: defective renal and intestinal transport of tryptophan Fast growing tumors can exhaust tryptophan supply Excess can cause high BP and uric acid, cardiac arrhythmias Can lower cholesterol

15. Rubin and Farber, Pathology - 2nd edition, p. 330

17. biotin Food sources and distribution: Can be synthesized by intestinal bacteria Found in most foods Signs and symptoms of deficiency Very rare, include dermatitis, muscle pain Toxicities, contraindications, and notes Chronic consumption of raw eggs can induce deficiency. Chronic inflammatory bowel disease can cause deficiency.

19. pantothenic (B5) Food sources and distribution: Ubiquitous Easily destroyed by heating Signs and symptoms of deficiency Very rare Neuromuscular degeneration Toxicities, contraindications and other notes Megadose can cause diarrhea and water retention

20. B-complex vitamins in energy metabolism and neuropathologies

21. Review B-complex vitamins and energy metabolism: Thiamine B1 TPP, pyruvate dehydrogenase Riboflavin B2 FAD, FADH2 Niacin B3 NAD+, NADH Pantothenic acid coenzyme A Biotin decarboxylation reactions (decarboxylase)

24. Pyridoxine (B6) Food sources and distribution: Meat, whole-grain breads and cereals, vegetables Signs and symptoms of deficiency Skin lesions Convulsive disorders resulting from low levels of GABA Needed for NAD+ synthesis Toxicities, contraindications and other notes Excess can lead to sensory nerve destruction, loss of feeling in fingers, legs Extra pyridoxine needed when using ISONAZIDE for treatment of TB ISONAZIDE binds covalently to pyridoxal phosphate

25. Champe and Harvey, p. 250

29. Stryer, Fig 29-16

30. Folic acid Food sources and distribution: Fresh green vegetables Cooking can destroy folic acid Signs and symptoms of deficiency Hemolytic anemias Toxicities, contraindications and other notes. Critical for pregnant women Megadose can interfere with Zinc absorption. May interfere with antiepileptic meds (phenobarbitol)

31. Rubin E, Pathology, p1379

32. Goodman Gilman, A. The Pharmacological Basis of Therapeutics, p.1245

33. Champe and Harvey, p. 327

35. Cobalamin (B12) Food sources and distribution: Synthesized only by microorganisms Deficiency usually results from absorption problem, not availability Signs and symptoms of deficiency: Pernicious anemia Megaloblastic anemia Neurologic dysfunction Can result in abnormal fatty acid accumulation in membranes Toxicities, contraindications and other notes Substantial stores of B12 are found in the body. Could take years to develop deficiency. Caution with patients who have had GI(gastro-intestinal) surgery.

36. Rubin and Farber, p. 1020

37. Vitamin C Food sources and distribution: Citrus fruits, potatoes Signs and symptoms of deficiency: Scurvy results from deficiency in collagen hydroxylation Results in spongy gums, loose teeth and bleeding under the skin Toxicities and contraindications: Can cause oxidation, particularly in presence of free metals Can be toxic with hemodialysis patients, iron storage diseases Ascorbate is metabolized to oxalate which can form insoluble precipitates with Ca++ Result in low Ca++, kidney stones, heart deposits.

39. Rubin and Farber, Pathology - 2nd edition, p. 333

41. Review: Diseases associated/resulting from deficiencies in water soluble vitamins: BeriBeri: Vit B1 Wernicke-Korsakoff syndrome: Vit B1 Pellagra: Vit B3 Pernicious anemia: B12 Megaloblastic anemia: B12 Scurvy: Vit C

42. Fat-soluble vitamins Vitamin A Vitamin D Vitamin E Vitamin K

43. Vitamin A Food sources and distribution: Low fat dairy products, deep yellow, orange vegetables Function: Vitamin A(retinol) is the precursor of retinel, the light-sensitive group in rhodopsin and other visual pigments. Signs and symptoms of deficiency: Night blindness, dry eyes and skin Slow growth in children Lowered resistance to infection Toxicities and contraindications: Overdose can result in dry skin, headache Can result in birth defects in pregnant women Can cause liver damage Vitamin A derivatives (isotretinoin, accutane) can cause birth defects and has been associated with suicide.

45. Rubin and Farber, Pathology - 2nd edition, p. 328

47. http://www.cnn.com/2002/US/01/08/plane.suicide.mother/index.htmlhttp://www.cnn.com/2002/US/01/08/plane.suicide.mother/index.html

48. Goodman and Gilman, The Pharmacological Basis of Therapeutics, p. 1599

49. Vitamin D Food sources and distribution: Egg yolks, fortified milk, fish oil, sun exposure Function: A metabolite of vitamin D is a hormone that regulates the metabolism of calcium and phosphorus. Signs and symptoms of deficiency: Rickets in children Osteomalacia (osteoporosis) in adults Toxicities and contraindications: The most toxic of vitamins in excess Calcium deposits in heart, hypertension, high cholesterol Fragile bones