2009 Cengage-Wadsworth Chapter 12 Microminerals

2009 Cengage-Wadsworth

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– Nonheme iron: nuts, fruits,

vegetables, grains, tofu, dairy– Grain foods fortified with iron


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


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


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


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


Iron

– Transport• Ferric Fe in blood - attached to transferrin• Ferrous Fe converted to ferric - catalyzed

by hephaestin (enterocytes) & ceruloplasmin (throughout body)

• Importance of transferrin


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


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


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


Iron

• Interactions with other nutrients– Vitamin C– Copper– Zinc– Vitamin A– Lead– Selenium


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


Iron

• Recommended Dietary Allowance– Men: 8 mg– Women: premenopausal 18 mg,

postmenopausal 8 mg– Pregnancy: 27 mg; lactation: 9 mg


Iron

• Deficiency: iron deficiency with & without anemia– Vulnerable:

• Infants/young children• Adolescents• Menstruating females• Pregnant women

– Supplements


Iron

• Toxicity: hemochromatosis– Mutations in HFE gene – Body cannot accurately sense iron

stores and down-regulate intestinal absorption


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


Zinc

• Sources– Red meats, seafood, poultry, pork,

dairy– Whole grains, vegetables– Availability affected by heat, Maillard

reaction products– Recycled from pancreatic & biliary

secretions


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


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


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


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


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


Zinc

– Other roles• Growth - regulation of transcription• Cell replication• Bone formation• Skin integrity• Cell-mediated immunity• Generalized host defense• Carbohydrate metabolism


Zinc

• Interactions with other nutrients– Vitamin A– Copper– Calcium– Cadmium

• Excretion– Mostly through GI tract– Small amount in urine & through skin

exfoliation/sweat


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


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


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


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


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


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


Copper

– Storage• Concentrates in liver, brain & kidneys• Stored bound to amino acids, proteins, &

chaperones• Metallothionein - stores up to 12 Cu

atoms


Copper

• Functions & mechanisms of action– Ceruloplasmin– Superoxide dismutase– Cytochrome c oxidase– Amine oxidases– Tyrosine metabolism--dopamin

monooxygenase & p-hydroxyphenylpyruvate hydroxylase


Copper

– Lysyl oxidase– Peptidylglycine alpha-amidating

monooxygenase– Other roles

• Angiogenesis• Immune system function• Nervy myelination• Endorphin action• Pro-oxidant• Influences gene expression


Copper

• Interactions with other nutrients– Ascorbic acid– Zinc– Iron– Molybdenum & sulfur (animals)– Selenium– Cadmium, silver, mercury


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


Copper

• Deficiency– Excessive zinc consumption,

nephrosis, GI malabsorption

• Toxicity– UL = 10 mg– Wilson’s disease– Supplements


Copper

• Assessment of nutriture– Serum/plasma/RBC Cu– Serum ceruloplasmin– Response of serum ceruloplasmin to

Cu supplements– Cu concentrations in hair not useful


Selenium

• Sources– Plant content variable based on soil– Seafood

• Absorption, transport, uptake, storage, & metabolism– Absorption

• Selenoamino acid absorption• Factors influencing selenium absorption


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


Selenium

– Metabolism• Selenomethionine• Selenocysteine• Free Se converted to selenide• Selenate converted to selenite to

selenodiglutathione to selenide


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


Selenium

• Interactions with other nutrients– Iron & copper– Methionine intake

• Excretion– About equally in urine & feces– Lungs & skin

• Exhalation of dimethylselenide


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


Selenium

• Toxicity– UL = 400 µg

• Assessment of nutriture– Blood & plasma concentrations– Activities & concentrations of

selenoproteins• SEL P, glutathione peroxidase

– Toenails, urinary concentration


Chromium

• Sources– Trivalent form - Cr3+

– Meats, fish, poultry, whole grains

• Absorption, transport, & storage– Absorption

• Small intestine, especially jejunum• Diffusion or by carrier-mediated

transporter


Chromium

– Factors influencing chromium absorption• Enhancers of chromium absorption

– Amino acids– Picolinate– Vitamin C

• Inhibitors of chromium absorption– Neutral or alkaline environment - antacids– Phytates


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


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


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


Chromium

• Deficiency– TPN, severe trauma & stress– Supplements

• Toxicity• Assessment of nutriture

– No specific tests– Observation of effects of Cr

supplementation


Iodine

• Sources– Food content variable based on soil– Seafoods, iodized salt


Iodine

• Digestion, absorption, transport, & storage– Organic bound I freed via digestion– Absorbed rapidly & completely– Travels as free iodide in blood– Concentrates in thyroid gland


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


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


Iodine

• Deficiency– Thyroid hormone release as related to

iodide deficiency– Iodine deficiency & iodine deficiency

disorders• Goiter• Iodine deficiency disorders (IDDs) • Cretinism: neurological or hypothyroid


Iodine

• Toxicity– UL = 1,100 µg

• Assessment of nutriture– Urinary excretion– Thyroid size– Radioactive iodide (131I) uptake– Serum TSH concentrations


Manganese

• Sources– Whole grains, dried fruits, nuts, leafy

vegetables


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


Manganese

• Functions & mechanisms of action– Transferases– Hydrolases– Lyases– Oxido-reductases– Ligases/synthetases– Other roles

• Modulator of second messenger pathways


Manganese

• Interactions with other nutrients– Iron; possibly calcium, zinc

• Excretion– Mostly in bile– Little in urine– Sweat, skin desquamation


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


Manganese

• Assessment of nutriture– Mononuclear blood cell/plasma/

serum/whole blood concentrations– Enzyme activity

• Lymphocyte Mn-SOD


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


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


Molybdenum

• Excretion– Most as molybdate in urine– Small amounts in bile, sweat, hair

• Recommended Dietary Allowance– Adults: 45 µg– Pregnancy/lactation: 50 µg


Molybdenum

• Deficiency– Diet rich in antagonistic substances

(e.g. sulfate, Cu, tungstate)

• Toxicity– UL = 2 mg

• Assessment of nutriture– No validated indicators


Fluoride

• Sources– Fluoridated water– Some grains, some marine fish– Tea


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


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


Fluoride

• Interactions with other nutrients– Aluminum, calcium, magnesium,

chloride

• Excretion– Mostly in urine, also feces, sweat

• Adequate Intake– Men: 4 mg; women: 3 mg


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


Perspective 12

Nutrient-Drug Interactions


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


Drug-Nutrient Interactions

• Effects of drugs on nutrient absorption

• Effects of drugs on nutrient metabolism

• Effects of drugs on nutrient excretion

• Summary

Documents

2009 Cengage-Wadsworth Chapter 12 Microminerals