1.  2009 Cengage-Wadsworth Chapter 12 Microminerals

2.  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

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

4.  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

5.  2009 Cengage-Wadsworth Iron –Nonheme iron digestion & absorption Hydrolyzed from food components in stomach Mostly ferric iron released into small intestine, some ferrous Fe 3+ may complex to ferric hydroxide Fe(OH) 3 - relatively insoluble Fe 2+ remains fairly soluble Fe 2+ absorbed via divalent cation transporter 1 (DMT1) Absorption of Fe 3+ increased by acidic environment & chelation of the iron

6.  2009 Cengage-Wadsworth Iron –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

7.  2009 Cengage-Wadsworth 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

8.  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

9.  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

10.  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

11.  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

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

13.  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

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

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

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

17.  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

18.  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

19.  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

20.  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

21.  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

22.  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

23.  2009 Cengage-Wadsworth Zinc 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

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

25.  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

26.  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

27.  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

28.  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

29.  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

30.  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

31.  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

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

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

34.  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

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

36.  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

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

38.  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

39.  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

40.  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

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

42.  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

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

44.  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

45.  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

46.  2009 Cengage-Wadsworth Chromium Sources –Trivalent form - Cr 3+ –Meats, fish, poultry, whole grains Absorption, transport, & storage –Absorption Small intestine, especially jejunum Diffusion or by carrier-mediated transporter

47.  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

48.  2009 Cengage-Wadsworth Chromium –Transport Cr 3+ 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

49.  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

50.  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

51.  2009 Cengage-Wadsworth Chromium Deficiency –TPN, severe trauma & stress –Supplements Toxicity Assessment of nutriture –No specific tests –Observation of effects of Cr supplementation

52.  2009 Cengage-Wadsworth Iodine Sources –Food content variable based on soil –Seafoods, iodized salt

53.  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

54.  2009 Cengage-Wadsworth Iodine Functions & mechanisms of action –Synthesis of thyroid hormones Thyroxine (T 4 ) Triiodothyronine (T 3 ) –Transport of thyroid hormones in the blood Thyroxine-binding globulin, albumin, transthyretin

55.  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

56.  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

57.  2009 Cengage-Wadsworth Iodine Toxicity –UL = 1,100 µg Assessment of nutriture –Urinary excretion –Thyroid size –Radioactive iodide ( 131 I) uptake –Serum TSH concentrations

58.  2009 Cengage-Wadsworth Manganese Sources –Whole grains, dried fruits, nuts, leafy vegetables

59.  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 Mn 2+ to alpha-2 macroglobulin, albumin, beta globulin, gamma globulin Accumulates in mitochondria

60.  2009 Cengage-Wadsworth Manganese Functions & mechanisms of action –Transferases –Hydrolases –Lyases –Oxido-reductases –Ligases/synthetases –Other roles Modulator of second messenger pathways

61.  2009 Cengage-Wadsworth Manganese Interactions with other nutrients –Iron; possibly calcium, zinc Excretion –Mostly in bile –Little in urine –Sweat, skin desquamation

62.  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

63.  2009 Cengage-Wadsworth Manganese Assessment of nutriture –Mononuclear blood cell/plasma/ serum/whole blood concentrations –Enzyme activity Lymphocyte Mn-SOD

64.  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 (MoO 4 2+ ) –Most found in liver, kidneys, bone

65.  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

66.  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

67.  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

68.  2009 Cengage-Wadsworth Fluoride Sources –Fluoridated water –Some grains, some marine fish –Tea

69.  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

70.  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

71.  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

72.  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

73.  2009 Cengage-Wadsworth Perspective 12 Nutrient-Drug Interactions

74.  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

75.  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