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Chapter 12

Chapter 12. Microminerals. Introduction. Precise definition of “essential micromineral” not established Sometimes defined as mineral needed in amounts of <100 mg/day RDAs established for 6 AIs for 3 others. Iron. Sources Heme iron: meat, fish, poultry

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Chapter 12

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  1. Chapter 12 Microminerals 2009 Cengage-Wadsworth

  2. Introduction • Precise definition of “essential micromineral” not established • Sometimes defined as mineral needed in amounts of <100 mg/day • RDAs established for 6 • AIs for 3 others 2009 Cengage-Wadsworth

  3. Iron • Sources • Heme iron: meat, fish, poultry • Nonheme iron: nuts, fruits, vegetables, grains, tofu, dairy • Grain foods fortified with iron 2009 Cengage-Wadsworth

  4. Iron • Digestion, absorption, transport, storage, & uptake • Heme iron digestion & absorption • Hydrolyzed from hemoglobin/myoglobin in stomach & small intestine • Heme absorbed intact by heme carrier protein 1 (hcp 1) • Hydrolyzed to inorganic ferrous Fe & protoporphyrin 2009 Cengage-Wadsworth

  5. Iron • Nonheme iron digestion & absorption • Hydrolyzed from food components in stomach • Mostly ferric iron released into small intestine, some ferrous • Fe3+ may complex to ferric hydroxide Fe(OH)3 - relatively insoluble • Fe2+ remains fairly soluble • Fe2+ absorbed via divalent cation transporter 1 (DMT1) • Absorption of Fe3+ increased by acidic environment & chelation of the iron 2009 Cengage-Wadsworth

  6. Factors influencing iron absorption Enhancers of iron absorption Sugars Acids (e.g. ascorbic, citric, lactic, tartaric) Meat, poultry fish Mucin Inhibitors of iron absorption Polyphenols Oxalic acid Phytates Phosvitin Calcium, calcium phosphate salts Zinc Manganese Nickel Iron 2009 Cengage-Wadsworth

  7. Iron • Intestinal cell iron use • 3 options • Transported through cytosol, across basolateril membrane to enter circulation • Stored for use or elimination • Used in a functional capacity • Regulation of iron absorption • Hepcidin • Ferroportin • Other basolateral membrane proteins 2009 Cengage-Wadsworth

  8. Iron • Transport • Ferric Fe in blood - attached to transferrin • Ferrous Fe converted to ferric - catalyzed by hephaestin (enterocytes) & ceruloplasmin (throughout body) • Importance of transferrin 2009 Cengage-Wadsworth

  9. Iron • Storage • Sites: liver, bone marrow, spleen • Storage proteins • Ferritin • H form or L form • Unstable - constantly degraded & resynthesized • Body & serum stores equalize • Hemosiderin • Increases during iron overload 2009 Cengage-Wadsworth

  10. Iron • Uptake by tissues • Affected by transferrin saturation level • Transferrin binds to transferrin receptors (TfR1, TfR2) to form a complex • Complex internalized into vesicle • Protons pumped in to reduce pH • Iron released from transferrin • Apotransferrin returned to plasma • # of receptors affected by intracelluar Fe 2009 Cengage-Wadsworth

  11. Iron • Functions & mechanisms of action • Hemoglobin & myoglobin • Cytochromes & other enzymes involved in electron transport • Monooxygenases & dioxygenases • Peroxidases • Oxidoreductases • Other iron-containing proteins • Iron as a pro-oxidant 2009 Cengage-Wadsworth

  12. Iron • Interactions with other nutrients • Vitamin C • Copper • Zinc • Vitamin A • Lead • Selenium 2009 Cengage-Wadsworth

  13. Iron • Turnover • Hemoglobin, ferritin & hemosiderin degradation yield plasma iron • Excretion • Most through GI tract (blood, bile, desquamated mucosal cells) • Skin (desquamation of surface cells) • Urine • Larger losses with hemorrhage, menses 2009 Cengage-Wadsworth

  14. Iron • Recommended Dietary Allowance • Men: 8 mg • Women: premenopausal 18 mg, postmenopausal 8 mg • Pregnancy: 27 mg; lactation: 9 mg 2009 Cengage-Wadsworth

  15. Iron • Deficiency: iron deficiency with & without anemia • Vulnerable: • Infants/young children • Adolescents • Menstruating females • Pregnant women • Supplements 2009 Cengage-Wadsworth

  16. Iron • Toxicity: hemochromatosis • Mutations in HFE gene • Body cannot accurately sense iron stores and down-regulate intestinal absorption 2009 Cengage-Wadsworth

  17. Iron • Assessment of nutriture - progression of deficiency • Serum ferritin decreases unless there is inflammation/infection • Ferritin & transferrin saturation decrease • Free protoporphyrin rises • Anemia occurs - hemoglobin & hematocrit typically altered • Blood cells indicators: MCV, MCH, MCHC 2009 Cengage-Wadsworth

  18. Zinc • Sources • Red meats, seafood, poultry, pork, dairy • Whole grains, vegetables • Availability affected by heat, Maillard reaction products • Recycled from pancreatic & biliary secretions 2009 Cengage-Wadsworth

  19. Zinc • Digestion, absorption, transport, uptake, & storage • Digestion • Hydrolyzed from amino/nucleic acids in stomach & small intestine • Absorption • Carrier-mediated process • Zrt- & Irt-like protein (ZIP) 4 • Passive diffusion & paracellular absorption with high intake 2009 Cengage-Wadsworth

  20. Zinc • Factors influencing zinc absorption • Enhancers of zinc absorption • Ligands - citric acid, picolinic acid, prostaglandins, amino acids • Low zinc status • Inhibitors of zinc absorption • Phytate • Oxalate • Polyphenols • Nutrients, e.g. folate, iron, calcium, copper 2009 Cengage-Wadsworth

  21. Zinc • Intestinal cell zinc use - may be: • Used functionally • Stored • Transported across basolateral membrane into plasma for transport • Transport • Blood - bound loosely to albumin • Also transferrin, alpha-2 macroglobulin, immunoglobulin G • Histidine, cysteine 2009 Cengage-Wadsworth

  22. Zinc • Uptake by tissues • ZIP carriers 1, 2, 4, 6, 7, 8, 14 • ZnT transporters • Distribution & storage • Found in all organs, especially liver, kidneys, muscle, skin, bones • Usually stored bound to thionein as metallothionein 2009 Cengage-Wadsworth

  23. Functions & mechanisms of action Zinc-dependent enzymes Carbonic anhydrase Alkaline phosphatase Alcohol dehydrogenase Carboxypeptidase Aminopeptidase Delta-aminolevulinic acid dehydratase Superoxide dismutase (SOD) Collagenases Phospholipase C Polyglutamate hydrolase Polymerases, kinases, nucleases, transferases, phosphorylases, transcriptases Zinc 2009 Cengage-Wadsworth

  24. Zinc • Other roles • Growth - regulation of transcription • Cell replication • Bone formation • Skin integrity • Cell-mediated immunity • Generalized host defense • Carbohydrate metabolism 2009 Cengage-Wadsworth

  25. Zinc • Interactions with other nutrients • Vitamin A • Copper • Calcium • Cadmium • Excretion • Mostly through GI tract • Small amount in urine & through skin exfoliation/sweat 2009 Cengage-Wadsworth

  26. Zinc • Recommended Dietary Allowance • Men: 11 mg; women: 8 mg • Pregnancy: 11 mg; lactation: 12 mg • Deficiency • Elderly & vegetarians • Needs increased by alcoholism, chronic illness, stress, trauama, surgery, malabsorption 2009 Cengage-Wadsworth

  27. Zinc • Supplements • Toxicity • UL = 40 mg • Assessment of nutriture • Zinc in RBCs, leukocytes, neutrophils, plasma/serum • Metallothionein concentrations • Urinary or hair zinc • Activity of zinc-dependent enzymes 2009 Cengage-Wadsworth

  28. Copper • Sources • Organ meats, shellfish • Nuts, seeds, legumes, dried fruits • Digestion, absorption, transport, uptake, & storage • Digestion • Bound to organic components in food • Released in stomach, small intestine 2009 Cengage-Wadsworth

  29. Copper • Absorption • Small amount via stomach (low pH) • Small intestine • Active carrier-mediated transporters • Nonsaturable, passive diffusion process • Transporters: Ctr1, DMT1 • Most reduced before absorption 2009 Cengage-Wadsworth

  30. Copper • Factors influencing copper absorption • Enchancers of copper absorption • Amino acids • Organic acids other than vitamin C • Inhibitors of copper absorption • Phytate • Zinc • Iron • Molybdenum • Calcium & phosphorus • Vitamin C • Excessive antacid ingestion/high pH 2009 Cengage-Wadsworth

  31. Copper • Intestinal cell copper use • Stored, used, or moved into blood • Transport & uptake • In blood: bound loosely to albumin or bound to transcuprein (Tc), amino acids • In liver: binds to metallothionein, then to apoceruloplasmin to form ceruloplasmin • Ceruloplasmin delivers Cu to tissues 2009 Cengage-Wadsworth

  32. Copper • Storage • Concentrates in liver, brain & kidneys • Stored bound to amino acids, proteins, & chaperones • Metallothionein - stores up to 12 Cu atoms 2009 Cengage-Wadsworth

  33. Copper • Functions & mechanisms of action • Ceruloplasmin • Superoxide dismutase • Cytochrome c oxidase • Amine oxidases • Tyrosine metabolism--dopamin monooxygenase & p-hydroxyphenylpyruvate hydroxylase 2009 Cengage-Wadsworth

  34. Copper • Lysyl oxidase • Peptidylglycine alpha-amidating monooxygenase • Other roles • Angiogenesis • Immune system function • Nervy myelination • Endorphin action • Pro-oxidant • Influences gene expression 2009 Cengage-Wadsworth

  35. Copper • Interactions with other nutrients • Ascorbic acid • Zinc • Iron • Molybdenum & sulfur (animals) • Selenium • Cadmium, silver, mercury 2009 Cengage-Wadsworth

  36. Copper • Excretion • Primarily through bile • Small amounts in urine, menstrual flow, hair, nails, semen • Involves P-type ATPase: ATP7B • Recommended Dietary Allowance • Adults: 900 µg • Pregnancy: 1,000 µg; lactation: 1,300 µg 2009 Cengage-Wadsworth

  37. Copper • Deficiency • Excessive zinc consumption, nephrosis, GI malabsorption • Toxicity • UL = 10 mg • Wilson’s disease • Supplements 2009 Cengage-Wadsworth

  38. Copper • Assessment of nutriture • Serum/plasma/RBC Cu • Serum ceruloplasmin • Response of serum ceruloplasmin to Cu supplements • Cu concentrations in hair not useful 2009 Cengage-Wadsworth

  39. Selenium • Sources • Plant content variable based on soil • Seafood • Absorption, transport, uptake, storage, & metabolism • Absorption • Selenoamino acid absorption • Factors influencing selenium absorption 2009 Cengage-Wadsworth

  40. Selenium • Transport • Bound to sulfhydryl groups in alpha & beta-globulins (e.g. VLDL, LDL) • Selenoprotein P • Uptake & storage • High concentrations in thyroid gland, kidney, liver, heart, pancreas, muscle • Also lungs, brain, bone, RBCs 2009 Cengage-Wadsworth

  41. Selenium • Metabolism • Selenomethionine • Selenocysteine • Free Se converted to selenide • Selenate converted to selenite to selenodiglutathione to selenide 2009 Cengage-Wadsworth

  42. Selenium • Functions & mechanisms of action • Glutathione peroxidase (GPX) • Thioredoxin reductase (TrxR or TRR) • Selenophosphate synthetase (SPS) • Selenoprotein P (SEL P) • Selenoprotein W (SEL W) • Methionine R sulfoxide reductase (SEL R) • Other selenoproteins • SEL 15; SEL S; SEL H, K, M, N 2009 Cengage-Wadsworth

  43. Selenium • Interactions with other nutrients • Iron & copper • Methionine intake • Excretion • About equally in urine & feces • Lungs & skin • Exhalation of dimethylselenide 2009 Cengage-Wadsworth

  44. Selenium • Recommended Dietary Allowance • Adults: 55 µg • Pregnancy: 60 µg; lactation: 70 µg • Deficiency • Keshan disease • Kashin-Beck’s disease • People on total parenteral nutrition 2009 Cengage-Wadsworth

  45. Selenium • Toxicity • UL = 400 µg • Assessment of nutriture • Blood & plasma concentrations • Activities & concentrations of selenoproteins • SEL P, glutathione peroxidase • Toenails, urinary concentration 2009 Cengage-Wadsworth

  46. Chromium • Sources • Trivalent form - Cr3+ • Meats, fish, poultry, whole grains • Absorption, transport, & storage • Absorption • Small intestine, especially jejunum • Diffusion or by carrier-mediated transporter 2009 Cengage-Wadsworth

  47. Chromium • Factors influencing chromium absorption • Enhancers of chromium absorption • Amino acids • Picolinate • Vitamin C • Inhibitors of chromium absorption • Neutral or alkaline environment - antacids • Phytates 2009 Cengage-Wadsworth

  48. Chromium • Transport • Cr3+ binds with transferrin in blood • No transferrin - albumin • Globulins, possibly lipoproteins • Storage • Concentrates in kidneys, liver, muscle, spleen, heart, pancrease, bone • Thought to be stored with ferric Fe 2009 Cengage-Wadsworth

  49. Chromium • Functions & mechanisms of action • Potentiates action of insulin • Glucose & lipid metabolism • Nucleic acid metabolism • Interactions with other nutrients • Potential to displace iron in transferrin unclear 2009 Cengage-Wadsworth

  50. Chromium • Excretion • Mostly in urine, also desquamation of skin cells • Adequate Intake • Adults 50 or < • Men: 35 µg; women: 25 µg • Adults >50 • Men: 30 µg; women: 20 µg • Pregnancy: 30 µg; lactation: 45 µg 2009 Cengage-Wadsworth

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