The Water-Soluble Vitamins

1. The Water-Soluble Vitamins B-vitamins and vitamin C

2. B Vitamins • Originally thought to be one vitamin • Actually, there are eight (maybe more) of them • Act primarily as coenzymes in metabolic pathways • Important for ATP production!!! • Important for MANY additional functions

3. B Vitamins • Dietary requirement is linked closely to metabolic rate (i.e., production) • Ruminant requirements met by rumen bacterial synthesis • Hindgut bacterial synthesis and absorption is insufficient to meet full requirements for a horse or most colonic fermenters • Caprophagy helps “recycle” and better utilize vitamins for cecal fermenters

4. B Vitamins - Sources • VARIETY of feedstuffs! • Plant sources • Found in fibrous portion of plants • Most cereals and grain products are enriched • Animal sources • Liver • Milk • Egg • Beef, pork and chicken

5. B Vitamin - Deficiency • LOTS of symptoms including fatigue • Specific diseases for each vitamin deficiency (e.g., beriberi, pellagra)

6. Thiamin (or Thiamine) • First vitamin to be discovered • Prevents beri-beri in humans • Anorexia, weakness, enlarged heart, edema • Thiamin pyrophosphate (TPP) is the active form of the vitamin (coenzyme) essential for carbohydrate and protein metabolism • Decarboxylation of ketoacids • Conversion of pyruvate to acetyl–CoA • Conversion of -ketoglutarate to succinate (TCA cycle) • Very heat labile – easily destroyed

7. Factors Affecting Thiamin Requirements • Carbohydrate intake • Thiaminase intake • Raw fish • Bracken fern poisoning in ruminants and horses • muscle tremor, incoordination, frequent falling, bradycardia and cardiac irregularity • Excess sulfur in ruminant diets(decreases thiamin synthesis)

8. Thiamin (B1) - Deficiency • Polyneuritis – retraction of head in chicks • In ruminants, polioencephalomalacia or “stargazing” (head retracted) • Cardiovascular disturbances • Beriberi – heart enlargement, numbness • Bradycardia – slow heart rate • Severe thiamin deficiency in alcohol abusers: Wernicke-Korsakoff syndrome • Disorientation • Loss of short term memory • Jerky eye movements • Staggering gait The limbic system (hippocampus, amygdale), parts of the diencephalons (mammillary bodies of the hypothalamus and dorsomedial nucleus within the thalamus), and parts of the basal forebrain (nucleus basalis of Meynert) all involved

9. Thiamin deficient chick on the right. Growth has been reduced due to interruption of the glycolytic pathway by lack of the coenzyme thiamin diphosphate.

10. Polyneuritis (“Stargazing”)

11. Thiamin Deficiency - Polyneuritis Thiamin-deficient rat shows typical arched back and hyperextended hind legs Same rat 8 hours after receiving thiamin hydrochloride has normal use of its hind legs and normal vestibular reaction

12. Thiamine Deficiency Peripheral Neuritis “Foot Drop” (A) Peripheral neuritis of nutritional origin shows limit of flexion of ankles (B) Moderate flexion is possible after 2 wk thiamine therapy A B

13. Thiamin Deficiency - Pitting Edema (A) Swelling of legs with pitting in ankle region marks beginning of so-called wet beriberi (B) 4 days after a single i.v. injection of thiamin A B

14. Thiamine Deficiency - Beriberi Heart A) Chronic alcoholic with extensive poor diet B) After 1 wk thiamine therapy C) After 3 wk treatment, reduction in heart size

15. Riboflavin (B2) - Sources • Milk and milk products • Enriched products • Liver

16. Riboflavin • Ribo: ribose Flavin: yellow • Component of flavoproteins • Component of the coenzymesflavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) • FMN  FMNH2 • FADH  FADH2 • Coenzymes for a wide variety of enzymes of intermediary metabolism • FADH is a hydrogen carrier in glycolysis, TCA and oxidative phosphorylation (electron transport chain)

17. Riboflavin • Absorbed by small intestine via active transport • Stable when heated • Breaks down in light and radiation • Milk sold in opaque/translucent containers

18. Riboflavin - Deficiency • Reduced growth • Ectodermal lesions • Curled-toe paralysis in birds • Due to nerve degeneration • Cataracts (swine) • Moon blindness in horses • Joint stiffness in swine • Ariboflavinosis • Inflammation of the mouth, skin, eyes, and GI tract

19. Curled Toe Paralysis

20. Riboflavin Deficiency (A) Generalized dermatitis & growth failure (B) After 1 month riboflavin treatment (C) After 2 months treatment

21. Niacin - Sources • Milk; eggs, meat, poultry, fish, • Whole grains and enriched products • All protein containing foods

22. Niacin • Occurs as nicotinic acid and nicotinamide • Body transforms nicotinic acid to nicotinamide, a major chemical form of niacin in the blood • Most mammals (except cats) can synthesize niacin from its precursor, tryptophan • Supplementation needed by all animals

23. Niacin - Functions • NAD and NADP are the main dietary forms of niacin • Heat-stable • Both are hydrolyzed by enzymes in the small intestinal mucosa to yield nicotinamide • Niacin can be synthesized from tryptophan • This process is not very efficient (60:1 tryptophan:niacin) • Niacin is essential for the formation of NAD and NADP (important in redox reactions) – THESE ARE THE ACTIVE FORMS OF THE VITAMIN • Nicotinamide adenine dinucleotide (NAD) acts as an electron acceptor in many biological redox reactions • NAD is a hydrogen carrier in glycolysis, TCA and oxidative phosphorylation (electron transport chain) • NADPH is a hydrogen donor in the synthesis of fatty acids

24. Niacin - Deficiency • Niacin in grain not available to monogastrics • Deficiency • Reduced growth and appetite • Black tongue – dog • Pellagra – farm animals and humans in “poor” areas of the world • Fiery inflammation of tongue, mouth and upper esophagus • Diarrhea, dermatitis, dementia, and death (the 4 D’s) • “Redneck” disease in niacin-deficient areas of the US • Major components of diet were the 3 M’s – meat (mostly pork fatback), molasses, and meal (corn meal) • Confusion, depression, poor memory

25. Discovering the Cause of Pellagra • High numbers of patients in insane asylums in the Southeast US in the first two decades of the 20th century suffered from pellagra – incidence rate reached epidemic proportions (3 million cases in the US alone) • Pellagra thought to be caused by contaminated corn or some infectious agent • Mississippi convict study (in exchange for a full pardon) • In 1915 Goldberger and 12 convict volunteers in Mississippi lived on a high-carbohydrate, high-fat, no-protein diet • All of the volunteers contracted pellagra • All were subsequently cured when their diets were changed • These findings were rejected by many scientists • Goldberger’s “filth parties” of 1916 (“Fifteen Men and a Housewife”) • Goldberger, several other “volunteers” (including his assistants), and his wife undertook the following procedures: • injecting the fresh blood of people sick with pellagra into their own bodies • swallowing vials bearing "little dough balls” impregnated with the urine and feces of sufferers • swallowing vials of dough balls combined with the scaled-off skin of the afflicted (cheek scrapings) None of those exposed contracted pellagra!

26. Early Pellagra - Glossitis Dental indentations resulting from edema - lip & tongue margins scarlet

27. Advanced Pellagra Dermatitis of elbows due to friction - beginning of desquamation in the center of lesion

29. Pellagra - Casal’s Collar or Necklace Photosensitive dermatitis outlining exposed area of neck & lesions on back of hands - sunlight or heat from a stove can induce this reaction Same patient after nicotinamide therapy

30. Pantothenic Acid • Food sources: • Organ meats • Whole grains • Legumes • Unstable in heat • Destroyed by food processing

31. Pantothenic Acid - Absorption • Coenzyme A (CoA) is the biologically active form of pantothenic acid • CoA from dietary sources is hydrolyzed in the intestinal lumen to pantothenic acid which is absorbed into the bloodstream by a Na+-dependent transporter

32. Pantothenic Acid - Functions • Part of co-enzyme A and acyl-carrier protein • Two-carbon carrier (ex., acetyl CoA) • Fatty-acid synthase complex

33. Pantothenic Acid - Functions • Essential for the synthesis of fatty acids and membrane phospholipids, including sphingolipids • Essential for oxidation of fatty acids and amino acids • Essential for the synthesis of steroid hormones • Essential for the synthesis of hemoglobin • CoA contributes an essential acetyl group during the synthesis of the neurotransmitter acetylcholine and to several glycoproteins and glycolipids

34. Pantothenic Acid - Deficiency • Deficiency is rare; “the burning feet” • Goose stepping - swine • Cannot bend hock joint (nervous system degeneration) • Reduced growth, dermatitis, diarrhea

35. Pantothenic acid deficiency - Chick Dermatitis in chick on pantothenic acid deficient diet Three weeks after calcium pantothenate added to diet, skin lesions cured

36. Pyridoxine (B6) - Sources • Meat, fish, poultry, liver • Non-citrus fruits • Legumes

37. Vitamin B6, Pyridoxine • Pyridoxine, pyrodixamine,and pyridoxal • Active form is coenzyme pyridoxal phosphate (PLP) • Exists in plants as pyridoxine or pyridoxal • Exists in animals as pyridoxamine or pyridoxal

38. Pyridoxine - Functions • Transamination processes • Create non-essential amino acids • Decarboxylation of amino acids • Energy from protein • Conversion of glycogen to glucose • Glycogen phosphorylase • Production of serotonin • Production of epinephrine and norepinephrine

39. Vitamin B6 • Function • Coenzyme for reactions in protein and nitrogen metabolism • Pyridoxyl phosphate (PLP) in transaminases • Red blood cell formation • Deficiency • Nervous system degeneration • Reduced antibody response • Symptoms include depression, confusion

40. Spontaneous Seborrheic Dermatitis Dermatitis around eyes, nose, mouth similar to that produced by pyridoxine antagonist Same patient after 3 weeks of pyridoxine ointment therapy

41. Pyridoxine Deficiency Edema & denuding of ears, paws & snout After3 weeks of pyridoxine hydrochloride

42. Cobalamin - Sources • Animal sources: meat, fish, poultry, eggs, shellfish, milk/products • Plant sources: none • Microbes!!

43. Vitamin B12, Cobalamin • Not synthesized by plants • “Animal-protein factor” • Often deficient in monogastric diets • Microbes synthesize B12 • Cobalt required • Some B12 synthesized in the hindgut • Not enough for most hind-gut fermenters, except horses

44. Cyanocobalamin (B12) • Active form is cyanide derivative of cobalamin - cyanocobalamin • Cobalt is an integral component • Close relationship between vitamin B12 and folate • Depend on each other for activation

45. Cobalamin Absorption • HCl and pepsin in the stomach release B12 from protein foods • Requires intrinsic factor for absorption • Secreted by parietal cells • Only essential function of stomach • Intrinsic factor attaches to B12 and the whole complex passes to the small intestine where the gradual absorption of B12 occurs

46. Vitamin B12 - Functions • Related to folic acid metabolism • Coenzyme for numerous reactions • Methylmalonyl CoA to succinyl CoA • DNA synthesis • Transmethylation (methionine synthesis)

47. Cobalamin - Functions • Vitamin B12 as a coenzyme is involved in the transfer of methyl groups to homocysteine to form methionine • It is also important for the methylation of uracil to form thymine which is converted to thymidine and used for DNA synthesis

48. Cobalamin - Deficiency • Deficiency often caused by inadequate absorption rather than poor intake • Lack of HCl or lack of intrinsic factor • Without HCl, the vitamin cannot be released from protein, and cannot attach to intrinsic factor • Atrophic gastritis: • Common in geriatric animals - stomach cells get damaged • Could also be due to iron deficiency or Helicobacter pylori • No healthy cells - decreased HCl and intrinsic factor • Result is pernicious anemia due to a combination of atrophic gastritis and lack of intrinsic factor • Other factors are defective gene for intrinsic factor, or if the stomach is injured or damaged

49. Cobalamin - Deficiency • Reduced growth • Anemia • Pernicious anemia in humans (lack intrinsic factor) • Macrocytic anemia (large red blood cells) • Neural symptoms • Wasting disease in ruminants (Co deficiency)

50. Cobalamin and Folate • High dose of folate masks B12 deficiency • In both deficiency states, the first symptom is that the blood cells grow rapidly • Either of the vitamins will be effective in resolving symptoms - however if folate is administered when B12 is needed, the situation will be disastrous • Results in devastating neurological symptoms • B12 deficiency leads to nerve damage caused by destruction of myelin sheaths that protect the nerves • Note: folate can clear the blood symptoms but cannot stop the nerve damage