Transcript Chapter 1
Chapter 9 The Water-Soluble Vitamins 2009 Cengage-Wadsworth 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 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 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 Vitamin C (Ascorbic Acid) – Microsomal metabolism – Antioxidant activity – Pro-oxidant activity – Other functions • Colds • Cancer • Cardiovascular disease • Cataracts 2009 Cengage-Wadsworth 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 Vitamin C (Ascorbic Acid) • Deficiency – Scurvy • Toxicity – UL = 2 g • Assessment of nutriture – Plasma & serum concentrations 2009 Cengage-Wadsworth 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 Thiamin (Vitamin B1) • Functions and mechanisms of action – Coenzyme roles • Energy transformation • Synthesis of pentoses & NADPH – Noncoenzyme roles: membrane & nerve conduction 2009 Cengage-Wadsworth 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 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 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, energydependent carrier mechanism in proximal small intestine 2009 Cengage-Wadsworth 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 Riboflavin (Vitamin B2) • Functions & mechanisms of action – Flavoproteins • Electron transport chain • Oxidative decarboxylation of pyruvate • Succinate dehydrogenase • Acyl CoA dehydrogenase • Sphinganine oxidase 2009 Cengage-Wadsworth • Xanthine oxidase • Aldehyde oxidase • Pyrodoxine phosphate oxidase • Active form of folate • Choline catabolism • Monoamine oxidase • Glutathione reductase • Thioredoxin reductase 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 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 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 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 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 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 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 Nadependent multivitamin transporter/ carrier (SMVT) 2009 Cengage-Wadsworth 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 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 Pantothenic Acid • Deficiency: burning feet syndrome • Toxicity – None reported • Assessment of nutriture – Blood concentrations – Urinary pantothenate excretion 2009 Cengage-Wadsworth 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 Biotin – From bacteria: absorbed in proximal & midtransverse colon – Absorption method • Pharmacologic doses: passive diffusion • Otherwise: SMVT – Transported in free, unbound state 2009 Cengage-Wadsworth 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 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 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 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 Folate – Reduced to THF in enterocytes, then metylated to 5-methyl THF or formylated – Transported in portal circulation as 5methyl THF – Found as a monoglutamate in blood 2009 Cengage-Wadsworth 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 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 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 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 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 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 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 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 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 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 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 Vitamin B6 • Functions & mechanisms of action • Cleavage • Racemization • Other synthetic reactions • Glycogen degradation – Coenzymes • Transmination • Decarboxylation • Transulfhydration & desulhydration • Dehydration (also called elimination) or deamination – Noncoenzyme role: steroid hormone action 2009 Cengage-Wadsworth 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 Vitamin B6 • Deficiency – Rare, but more likely in elderly, alcoholics, people on certain drugs • Toxicity – Sensory & peripheral neuropathy – UL = 100 mg 2009 Cengage-Wadsworth 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 Perspective 9 Genetics & Nutrition: The Possible Effect on Human Folate Needs & Risk to Chronic Disease 2009 Cengage-Wadsworth 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