Transcript Chapter 1
Chapter 12 Microminerals 2009 Cengage-Wadsworth 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 Iron • Sources – Heme iron: meat, fish, poultry – Nonheme iron: nuts, fruits, vegetables, grains, tofu, dairy – Grain foods fortified with iron 2009 Cengage-Wadsworth 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 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 Iron – Factors influencing iron absorption • Enhancers of iron absorption – Sugars – Acids (e.g. ascorbic, citric, lactic, tartaric) – Meat, poultry fish – Mucin 2009 Cengage-Wadsworth • Inhibitors of iron absorption – – – – – Polyphenols Oxalic acid Phytates Phosvitin Calcium, calcium phosphate salts – Zinc – Manganese – Nickel 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 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 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 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 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 Iron • Interactions with other nutrients – Vitamin C – Copper – Zinc – Vitamin A – Lead – Selenium 2009 Cengage-Wadsworth 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 Iron • Recommended Dietary Allowance – Men: 8 mg – Women: premenopausal 18 mg, postmenopausal 8 mg – Pregnancy: 27 mg; lactation: 9 mg 2009 Cengage-Wadsworth Iron • Deficiency: iron deficiency with & without anemia – Vulnerable: • Infants/young children • Adolescents • Menstruating females • Pregnant women – Supplements 2009 Cengage-Wadsworth Iron • Toxicity: hemochromatosis – Mutations in HFE gene – Body cannot accurately sense iron stores and down-regulate intestinal absorption 2009 Cengage-Wadsworth 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 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 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 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 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 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 Zinc • Functions & mechanisms of action – Zinc-dependent enzymes • Carbonic anhydrase • Alkaline phosphatase • Alcohol dehydrogenase 2009 Cengage-Wadsworth • Carboxypeptidase • Aminopeptidase • Delta-aminolevulinic acid dehydratase • Superoxide dismutase (SOD) • Collagenases • Phospholipase C • Polyglutamate hydrolase • Polymerases, kinases, nucleases, transferases, phosphorylases, transcriptases Zinc – Other roles • Growth - regulation of transcription • Cell replication • Bone formation • Skin integrity • Cell-mediated immunity • Generalized host defense • Carbohydrate metabolism 2009 Cengage-Wadsworth 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 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 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 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 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 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 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 Copper – Storage • Concentrates in liver, brain & kidneys • Stored bound to amino acids, proteins, & chaperones • Metallothionein - stores up to 12 Cu atoms 2009 Cengage-Wadsworth Copper • Functions & mechanisms of action – Ceruloplasmin – Superoxide dismutase – Cytochrome c oxidase – Amine oxidases – Tyrosine metabolism--dopamin monooxygenase & phydroxyphenylpyruvate hydroxylase 2009 Cengage-Wadsworth 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 Copper • Interactions with other nutrients – Ascorbic acid – Zinc – Iron – Molybdenum & sulfur (animals) – Selenium – Cadmium, silver, mercury 2009 Cengage-Wadsworth 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 Copper • Deficiency – Excessive zinc consumption, nephrosis, GI malabsorption • Toxicity – UL = 10 mg – Wilson’s disease – Supplements 2009 Cengage-Wadsworth 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 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 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 Selenium – Metabolism • Selenomethionine • Selenocysteine • Free Se converted to selenide • Selenate converted to selenite to selenodiglutathione to selenide 2009 Cengage-Wadsworth 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 Selenium • Interactions with other nutrients – Iron & copper – Methionine intake • Excretion – About equally in urine & feces – Lungs & skin • Exhalation of dimethylselenide 2009 Cengage-Wadsworth 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 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 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 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 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 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 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 Chromium • Deficiency – TPN, severe trauma & stress – Supplements • Toxicity • Assessment of nutriture – No specific tests – Observation of effects of Cr supplementation 2009 Cengage-Wadsworth Iodine • Sources – Food content variable based on soil – Seafoods, iodized salt 2009 Cengage-Wadsworth Iodine • Digestion, absorption, transport, & storage – Organic bound I freed via digestion – Absorbed rapidly & completely – Travels as free iodide in blood – Concentrates in thyroid gland 2009 Cengage-Wadsworth Iodine • Functions & mechanisms of action – Synthesis of thyroid hormones • Thyroxine (T4) • Triiodothyronine (T3) – Transport of thyroid hormones in the blood • Thyroxine-binding globulin, albumin, transthyretin 2009 Cengage-Wadsworth Iodine • Interactions with other nutrients – Goitrogens • Excretion – Most in urine, also in feces • Recommended Dietary Allowance – Adults: 150 µg – Pregnancy: 220 µg; lactation: 290 µg 2009 Cengage-Wadsworth Iodine • Deficiency – Thyroid hormone release as related to iodide deficiency – Iodine deficiency & iodine deficiency disorders • Goiter • Iodine deficiency disorders (IDDs) • Cretinism: neurological or hypothyroid 2009 Cengage-Wadsworth Iodine • Toxicity – UL = 1,100 µg • Assessment of nutriture – Urinary excretion – Thyroid size – Radioactive iodide (131I) uptake – Serum TSH concentrations 2009 Cengage-Wadsworth Manganese • Sources – Whole grains, dried fruits, nuts, leafy vegetables 2009 Cengage-Wadsworth Manganese • Absorption, transport, & storage – Absorption • Probably low-capacity, high affinity, active transport mechanism • Factors influencing absorption – Fiber, phytate, oxalate, iron, copper – Transport & storage • Free or bound as Mn2+ to alpha-2 macroglobulin, albumin, beta globulin, gamma globulin • Accumulates in mitochondria 2009 Cengage-Wadsworth Manganese • Functions & mechanisms of action – Transferases – Hydrolases – Lyases – Oxido-reductases – Ligases/synthetases – Other roles • Modulator of second messenger pathways 2009 Cengage-Wadsworth Manganese • Interactions with other nutrients – Iron; possibly calcium, zinc • Excretion – Mostly in bile – Little in urine – Sweat, skin desquamation 2009 Cengage-Wadsworth Manganese • Adequate Intake – Men: 2.3 mg; women: 1.8 mg – Pregnancy: 2 mg; lactation: 2.6 mg • Deficiency • Toxicity – Liver failure, neonatal TPN – Miners who inhale Mn dust – UL = 11 mg 2009 Cengage-Wadsworth Manganese • Assessment of nutriture – Mononuclear blood cell/plasma/ serum/whole blood concentrations – Enzyme activity • Lymphocyte Mn-SOD 2009 Cengage-Wadsworth Molybdenum • Sources – Legumes, meat, fish, poultry, grains • Absorption, transport, & storage – Thought to be passive absorption – Thought to travel in blood as molybdate (MoO42+) – Most found in liver, kidneys, bone 2009 Cengage-Wadsworth Molybdenum • Functions & mechanisms of action – Sulfite oxidase – Aldehyde oxidase – Xanthine dehydrogenase & xanthine oxidase • Interactions with other nutrients – Tungsten – Sulfur & copper – Manganese, zinc, iron, lead, ascorbic acid, methionine, cysteine, protein 2009 Cengage-Wadsworth Molybdenum • Excretion – Most as molybdate in urine – Small amounts in bile, sweat, hair • Recommended Dietary Allowance – Adults: 45 µg – Pregnancy/lactation: 50 µg 2009 Cengage-Wadsworth Molybdenum • Deficiency – Diet rich in antagonistic substances (e.g. sulfate, Cu, tungstate) • Toxicity – UL = 2 mg • Assessment of nutriture – No validated indicators 2009 Cengage-Wadsworth Fluoride • Sources – Fluoridated water – Some grains, some marine fish – Tea 2009 Cengage-Wadsworth Fluoride • Digestion, absorption, transport, & storage – Protein-bound F hydrolyzed – Thought to be absorbed by passive diffusion (rapid in stomach) – Transported as ionic F or hydrofluoric acid, or bound (nonionic/organic) – Most found in bones & teeth 2009 Cengage-Wadsworth Fluoride • Functions & mechanisms of action – Promotes mineral precipitation from amorphous solutions of Ca & phosphate - formation of apatite – Can replace hydroxide ions in apatite – Topical F appears to decrease production of acid by oral bacteria 2009 Cengage-Wadsworth Fluoride • Interactions with other nutrients – Aluminum, calcium, magnesium, chloride • Excretion – Mostly in urine, also feces, sweat • Adequate Intake – Men: 4 mg; women: 3 mg 2009 Cengage-Wadsworth Fluoride • Deficiency • Toxicity – Fluorosis – UL = 1.3 mg for children 1-3 – 10 mg for children >8 & adults • Assessment of nutriture – Plasma or urine concentrations – Ion-specific electrode potentiometry 2009 Cengage-Wadsworth Perspective 12 Nutrient-Drug Interactions 2009 Cengage-Wadsworth Nutrient-Drug Interactions • Effects of foods/nutrients on drug absorption • Effects of foods on drug metabolism • Effects of foods/nutrients on the actions of drugs • Effects of foods/nutrients on drug excretion 2009 Cengage-Wadsworth Drug-Nutrient Interactions • Effects of drugs on nutrient absorption • Effects of drugs on nutrient metabolism • Effects of drugs on nutrient excretion • Summary 2009 Cengage-Wadsworth