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Chapter 9

Chapter 9. The Water-Soluble Vitamins. General Characteristics of Vitamins. Organic compounds with regulatory functions Essential in the diet Water-soluble & fat-soluble handled differently in the body DRIs estimate needed intakes RDAs, AIs, ULs, & EARs . Vitamin C (Ascorbic Acid).

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Chapter 9

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  1. Chapter 9 The Water-Soluble Vitamins 2009 Cengage-Wadsworth

  2. General Characteristics of Vitamins • Organic compounds with regulatory functions • Essential in the diet • Water-soluble & fat-soluble handled differently in the body • DRIs estimate needed intakes • RDAs, AIs, ULs, & EARs 2009 Cengage-Wadsworth

  3. Vitamin C (Ascorbic Acid) • Sources • Fruits & vegetables • Digestion, absorption, transport, & storage • No digestion required • Absorption by SVCT1 & SVCT2 • Oxidation prior to absorption • Absorption decreases with intake • Transported primarily in free form 2009 Cengage-Wadsworth

  4. Vitamin C (Ascorbic Acid) • Functions and mechanisms of action • Collagen synthesis • Carnitine synthesis • Tyrosine synthesis & catabolism • Neurotransmitter synthesis • Norepinephrine • Serotonin • Other neurotransmitters & hormones 2009 Cengage-Wadsworth

  5. Vitamin C (Ascorbic Acid) • Microsomal metabolism • Antioxidant activity • Pro-oxidant activity • Other functions • Colds • Cancer • Cardiovascular disease • Cataracts 2009 Cengage-Wadsworth

  6. Vitamin C (Ascorbic Acid) • Interactions with other nutrients • Iron • Copper • Metabolism and excretion • Excreted or oxidized to dehydroascorbate • Recommended Dietary Allowance • Men: 90 mg; women: 75 mg • Pregnancy: 100 mg; lactation: 120 mg • + 35 mg for smokers 2009 Cengage-Wadsworth

  7. Vitamin C (Ascorbic Acid) • Deficiency • Scurvy • Toxicity • UL = 2 g • Assessment of nutriture • Plasma & serum concentrations 2009 Cengage-Wadsworth

  8. Thiamin (Vitamin B1) • Sources • Meats, legumes, grains • Digestion, absorption, transport, & storage • Antithiamin factors • Absorption in jejunum, by diffusion or carriers: ThTr1 & ThTr2 • Ethanol interferes • Transported free, bound to albumin, or as thiamine monophosphate (TMP) 2009 Cengage-Wadsworth

  9. Thiamin (Vitamin B1) • Functions and mechanisms of action • Coenzyme roles • Energy transformation • Synthesis of pentoses & NADPH • Noncoenzyme roles: membrane & nerve conduction 2009 Cengage-Wadsworth

  10. Thiamin (Vitamin B1) • Metabolism & excretion • Excreted intact or catabolized • Recommended Dietary Allowance • Men: 1.2 mg; women: 1.1 mg • Pregnancy: 1.4 mg; lactation: 1.5 mg • Deficiency: beriberi • Dry beriberi • Wet beriberi • Acute beriberi • Wernicke-Korsakoff syndrome 2009 Cengage-Wadsworth

  11. Thiamin (Vitamin B1) • Toxicity • Little danger with oral intake; no UL • Assessment of nutriture • Measuring erythrocyte transketolase activity in whole blood • Measuring thiamine in blood or urine 2009 Cengage-Wadsworth

  12. Riboflavin (Vitamin B2) • Sources • Milk/dairy, eggs, meat, legumes • Digestion, absorption, transport, & storage • Riboflavin as FAD, FMN & riboflavin phosphate freed prior to absorption • Absorbed by saturable, energy-dependent carrier mechanism in proximal small intestine 2009 Cengage-Wadsworth

  13. Riboflavin (Vitamin B2) • Phosphorylated to FMN & then dephosphorylated back to riboflavin • Riboflavin transported to liver for conversion to FMN & FAD • Most flavins in systemic plasma are riboflavin 2009 Cengage-Wadsworth

  14. Functions & mechanisms of action Flavoproteins Electron transport chain Oxidative decarboxylation of pyruvate Succinate dehydrogenase Acyl CoA dehydrogenase Sphinganine oxidase Xanthine oxidase Aldehyde oxidase Pyrodoxine phosphate oxidase Active form of folate Choline catabolism Monoamine oxidase Glutathione reductase Thioredoxin reductase Riboflavin (Vitamin B2) 2009 Cengage-Wadsworth

  15. Riboflavin (Vitamin B2) • Metabolism & excretion • Excreted primarily in urine; small amount in feces • Recommended Dietary Allowance • Men: 1.3 mg; women 1.1 mg • Pregnancy: 1.4 mg; lactation: 1.6 mg 2009 Cengage-Wadsworth

  16. Riboflavin (Vitamin B2) • Deficiency: ariboflavinosis • Toxicity • None reported; no UL • Assessment of nutriture • Measuring activity of erythrocyte glutathione reductase • Cellular & urinary concentrations 2009 Cengage-Wadsworth

  17. Niacin (Vitamin B3) • Sources • Fish, meats, grains, seeds, legumes • Synthesis in liver from tryptophan • Digestion, absorption, transport, & storage • NAD & NADP hyrolyzed to free nicotinamide • Absorbed in small intestine & stomach • Absorbed mostly by passive diffusion • Transported primarily as nicotinamide, & as nicotinic acid 2009 Cengage-Wadsworth

  18. Niacin (Vitamin B3) • Functions & mechanisms of action • Coenzymes • Oxidative reactions • Reductive biosynthesis • Folate metabolism • Nonredox roles • Donor of ADP-ribose for posttranslational modification of proteins & formation of cyclic ADP-ribose 2009 Cengage-Wadsworth

  19. Niacin (Vitamin B3) • Metabolism & excretion • NAD/NADP degraded to nicotinamide & ADP-ribose • Nicotinamide methylated & oxidized in liver to products excreted in urine • Recommended Daily Allowance • Men: 16 mg NE; women 14 mg NE • Pregnancy: 18 mg NE; lactation: 17 mg NE 2009 Cengage-Wadsworth

  20. Niacin (Vitamin B3) • Deficiency: pellagra • Toxicity • Large doses used to treat hypercholesterolemia • Side effects with doses >1 g/day • UL = 35 mg • Assessment of nutriture • Measuring urinary metabolites • Erythrocyte NAC concentrations • Ratio of NAD to NADP 2009 Cengage-Wadsworth

  21. Pantothenic Acid • Sources - virtually all foods • Digestion, absorption, transport, & storage • CoA form hydrolyzed to free form • Absorbed principally in jejunum by passive diffusion • Low concentrations - absorbed by Na-dependent multivitamin transporter/ carrier (SMVT) 2009 Cengage-Wadsworth

  22. Pantothenic Acid • Transported in free form in blood • Functions & mechanisms of action • Component of CoA & 4’-phophopantetheine • Nutrient metabolism • Prosthetic group for actyl carrier protein (ACP) - FA synthesis • Acetylation of proteins, sugars, drugs 2009 Cengage-Wadsworth

  23. Pantothenic Acid • Metabolism & excretion • Excreted intact in urine, small amounts in feces • Adequate Intake • Adults: 5 mg • Pregnancy: 6 mg; lactation: 7 mg 2009 Cengage-Wadsworth

  24. Pantothenic Acid • Deficiency: burning feet syndrome • Toxicity • None reported • Assessment of nutriture • Blood concentrations • Urinary pantothenate excretion 2009 Cengage-Wadsworth

  25. Biotin • Sources • Widely distributed in foods • Made by large intestinal bacteria • Digestion, absorption, transport, & storage • Protein-bound: digestion by proteolytic enzymes • From food: absorbed primarily in jejunum, followed by ileum 2009 Cengage-Wadsworth

  26. Biotin • From bacteria: absorbed in proximal & midtransverse colon • Absorption method • Pharmacologic doses: passive diffusion • Otherwise: SMVT • Transported in free, unbound state 2009 Cengage-Wadsworth

  27. Biotin • Functions & mechanisms of action • Coenzyme roles • Pyruvate carboxylase • Acetyl CoA carboxylase • Propionyl CoA carboxylase • -methylcrotonyl CoA carboxylase • Non-coenzyme roles • Cell proliferation, gene silencing, & DNA repair • Gene expression & cell signaling 2009 Cengage-Wadsworth

  28. Biotin • Metabolism & excretion • Biotin holocarboxylases catabolyzed to biotin oligopeptides & then biocytin • Biocytin degraded to lysine & biotin • Metabolites excreted in urine • Biotin from bacteria that is not absorbed excreted in feces 2009 Cengage-Wadsworth

  29. Biotin • Adequate Intake • Adults & pregnancy: 30 µg • Lactation: 35 µg • Deficiency • Rare but serious • Toxicity • None reported • Assessment of nutriture • Urinary excretion is a sensitive indicator 2009 Cengage-Wadsworth

  30. Folate • Sources • Mushrooms, green vegetables, peanuts, legumes, lentils, fruits, liver • Digestion, absorption, transport, & storage • Polyglutamate forms hydrolyzed to monoglutamate form • Absorbed with folate-binding proteins 2009 Cengage-Wadsworth

  31. Folate • Reduced to THF in enterocytes, then metylated to 5-methyl THF or formylated • Transported in portal circulation as 5-methyl THF • Found as a monoglutamate in blood 2009 Cengage-Wadsworth

  32. Folate • Functions & mechanisms of action • Amino acid metabolism • Histidine • Serine & glycine • Methionine • Possible relationship with diseases • Purine & pyrimidine synthesis/ nucleotide metabolism • Other relationships with diseases 2009 Cengage-Wadsworth

  33. Folate • Interactions with other nutrients • Vitamin B12 • Metabolism & excretion • Excreted in urine & feces • Recommended Dietary Allowance • Adults: 400 µg DFE • Pregnancy: 600 µg DFE; lactation 500 µg DFE 2009 Cengage-Wadsworth

  34. Folate • Deficiency: megaloblastic macrocytic anemia • Toxicity • UL = 1 mg synthetic (non-natural) • Assessment of nutriture • Plasma, serum or RBC concentration • N-formiminoglutamate excretion • Deoxyuridine suppression test 2009 Cengage-Wadsworth

  35. Vitamin B12 (Cobalamin) • Sources - animal products • Digestion, absorption, transport, & storage • In the stomach • Released from proteins/polypeptides • Binds to an R protein 2009 Cengage-Wadsworth

  36. Vitamin B12 (Cobalamin) • In the duodenum • R protein hydrolyzed - free cobalamin • Binds to intrinsic factor • In the ileum • Absorbed via binding with receptors (cubilins) • Binds to transcobalamin II for transport • Enterohepatic circulation 2009 Cengage-Wadsworth

  37. Vitamin B12 (Cobalamin) • In blood, bound to 1 of 3 cobalamins • TCII - main protein that carries newly absorbed cobalamin in 1-1 ratio • TCI & TCIII - exact functions unknown • Can be stored & retained in the body for long periods 2009 Cengage-Wadsworth

  38. Vitamin B12 (Cobalamin) • Functions & mechanisms of action • Conversion of homocysteine to methionine (methylcobalamin) • Conversion of L-methylmalonyl CoA to succinyl CoA (adenosylcobalamin) • Metabolism & excretion • 0.1%/day excreted in bile, bound to R protein 2009 Cengage-Wadsworth

  39. Vitamin B12 (Cobalamin) • Recommended Dietary Allowance • Adults: 2.4 µg • Pregnancy: 2.6 µg; lactation: 2.8 µg • Deficiency: megaloblastic macrocytic anemia • Also neuropathy • Usually caused by inadequate absorption 2009 Cengage-Wadsworth

  40. Vitamin B12 (Cobalamin) • Toxicity • None observed • Assessment of nutriture • Serum concentrations • Serum methylmalonyl CoA or methylmalonic acid & homocysteine • Doxyuridine supression test • Schilling test 2009 Cengage-Wadsworth

  41. Vitamin B6 • Sources • Meats, whole grains, vegetables, some fruits, nuts • Digestion, absorption, transport, & storage • Dephosphorylated to PN, PL, or PM • Primarily absorbed by passive diffusion in jejunum 2009 Cengage-Wadsworth

  42. Vitamin B6 • PN, PL & PM released into portal blood • Most converted to PLP in liver • Most PLP transported bound to albumin • PL, PN, PM & PMP also found in blood 2009 Cengage-Wadsworth

  43. Functions & mechanisms of action Coenzymes Transmination Decarboxylation Transulfhydration & desulhydration Dehydration (also called elimination) or deamination Cleavage Racemization Other synthetic reactions Glycogen degradation Noncoenzyme role: steroid hormone action Vitamin B6 2009 Cengage-Wadsworth

  44. Vitamin B6 • Metabolism & excretion • 4-pyridoxic acid (PIC) - metabolite • Excreted in urine • Recommended Dietary Allowance • Men 19-50: 1.3 mg; 51 & >: 1.7 mg • Women 19-50: 1.3 mg; 51 & >: 1.5 mg • Pregnancy: 1.9 mg; lactation: 2.0 mg 2009 Cengage-Wadsworth

  45. Vitamin B6 • Deficiency • Rare, but more likely in elderly, alcoholics, people on certain drugs • Toxicity • Sensory & peripheral neuropathy • UL = 100 mg 2009 Cengage-Wadsworth

  46. Vitamin B6 • Assessment of nutriture • Plasma PLP concentrations • Xanthurenic acid excretion following tryptophan loading • Urinary B6 & 4-pyridoxic acid • Erythrocyte transaminase activity before & after adding B6 2009 Cengage-Wadsworth

  47. Perspective 9 Genetics & Nutrition:The Possible Effect on Human Folate Needs & Risk to Chronic Disease 2009 Cengage-Wadsworth

  48. Genetics & Nutrition • Introduction • N5,N10 methylenetetrahydrofolate reductase & its genetic variants • Ethnic differences in genetic variations in MTHFR • MTHFR variations & risk to chronic disease • Summary 2009 Cengage-Wadsworth

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