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Chapter 12
Microminerals
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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
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Iron
• Sources
– Heme iron: meat, fish, poultry
– Nonheme iron: nuts, fruits,
vegetables, grains, tofu, dairy
– Grain foods fortified with iron
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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
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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
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Iron
– Factors influencing
iron absorption
• Enhancers of iron
absorption
– Sugars
– Acids (e.g.
ascorbic, citric,
lactic, tartaric)
– Meat, poultry fish
– Mucin
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• 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
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Iron
– Transport
• Ferric Fe in blood - attached to
transferrin
• Ferrous Fe converted to ferric - catalyzed
by hephaestin (enterocytes) &
ceruloplasmin (throughout body)
• Importance of transferrin
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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
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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
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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
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Iron
• Interactions with other nutrients
– Vitamin C
– Copper
– Zinc
– Vitamin A
– Lead
– Selenium
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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
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Iron
• Recommended Dietary Allowance
– Men: 8 mg
– Women: premenopausal 18 mg,
postmenopausal 8 mg
– Pregnancy: 27 mg; lactation: 9 mg
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Iron
• Deficiency: iron deficiency with &
without anemia
– Vulnerable:
• Infants/young children
• Adolescents
• Menstruating females
• Pregnant women
– Supplements
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Iron
• Toxicity: hemochromatosis
– Mutations in HFE gene
– Body cannot accurately sense iron
stores and down-regulate intestinal
absorption
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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
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Zinc
• Sources
– Red meats, seafood, poultry, pork,
dairy
– Whole grains, vegetables
– Availability affected by heat, Maillard
reaction products
– Recycled from pancreatic & biliary
secretions
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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
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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
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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
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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
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Zinc
• Functions &
mechanisms of
action
– Zinc-dependent
enzymes
• Carbonic
anhydrase
• Alkaline
phosphatase
• Alcohol
dehydrogenase
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• 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
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Zinc
• Interactions with other nutrients
–
–
–
–
Vitamin A
Copper
Calcium
Cadmium
• Excretion
– Mostly through GI tract
– Small amount in urine & through skin
exfoliation/sweat
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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
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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
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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
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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
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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
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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
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Copper
– Storage
• Concentrates in liver, brain & kidneys
• Stored bound to amino acids, proteins, &
chaperones
• Metallothionein - stores up to 12 Cu
atoms
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Copper
• Functions & mechanisms of action
– Ceruloplasmin
– Superoxide dismutase
– Cytochrome c oxidase
– Amine oxidases
– Tyrosine metabolism--dopamin
monooxygenase & phydroxyphenylpyruvate hydroxylase
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Copper
– Lysyl oxidase
– Peptidylglycine alpha-amidating
monooxygenase
– Other roles
•
•
•
•
•
•
Angiogenesis
Immune system function
Nervy myelination
Endorphin action
Pro-oxidant
Influences gene expression
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Copper
• Interactions with other nutrients
– Ascorbic acid
– Zinc
– Iron
– Molybdenum & sulfur (animals)
– Selenium
– Cadmium, silver, mercury
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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
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Copper
• Deficiency
– Excessive zinc consumption,
nephrosis, GI malabsorption
• Toxicity
– UL = 10 mg
– Wilson’s disease
– Supplements
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Copper
• Assessment of nutriture
– Serum/plasma/RBC Cu
– Serum ceruloplasmin
– Response of serum ceruloplasmin to
Cu supplements
– Cu concentrations in hair not useful
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Selenium
• Sources
– Plant content variable based on soil
– Seafood
• Absorption, transport, uptake,
storage, & metabolism
– Absorption
• Selenoamino acid absorption
• Factors influencing selenium absorption
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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
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Selenium
– Metabolism
• Selenomethionine
• Selenocysteine
• Free Se converted to selenide
• Selenate converted to selenite to
selenodiglutathione to selenide
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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
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Selenium
• Interactions with other nutrients
– Iron & copper
– Methionine intake
• Excretion
– About equally in urine & feces
– Lungs & skin
• Exhalation of dimethylselenide
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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
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Selenium
• Toxicity
– UL = 400 µg
• Assessment of nutriture
– Blood & plasma concentrations
– Activities & concentrations of
selenoproteins
• SEL P, glutathione peroxidase
– Toenails, urinary concentration
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Chromium
• Sources
– Trivalent form - Cr3+
– Meats, fish, poultry, whole grains
• Absorption, transport, & storage
– Absorption
• Small intestine, especially jejunum
• Diffusion or by carrier-mediated
transporter
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Chromium
– Factors influencing chromium
absorption
• Enhancers of chromium absorption
– Amino acids
– Picolinate
– Vitamin C
• Inhibitors of chromium absorption
– Neutral or alkaline environment - antacids
– Phytates
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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
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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
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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
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Chromium
• Deficiency
– TPN, severe trauma & stress
– Supplements
• Toxicity
• Assessment of nutriture
– No specific tests
– Observation of effects of Cr
supplementation
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Iodine
• Sources
– Food content variable based on soil
– Seafoods, iodized salt
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Iodine
• Digestion, absorption, transport, &
storage
– Organic bound I freed via digestion
– Absorbed rapidly & completely
– Travels as free iodide in blood
– Concentrates in thyroid gland
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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
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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
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Iodine
• Deficiency
– Thyroid hormone release as related to
iodide deficiency
– Iodine deficiency & iodine deficiency
disorders
• Goiter
• Iodine deficiency disorders (IDDs)
• Cretinism: neurological or hypothyroid
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Iodine
• Toxicity
– UL = 1,100 µg
• Assessment of nutriture
– Urinary excretion
– Thyroid size
– Radioactive iodide (131I) uptake
– Serum TSH concentrations
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Manganese
• Sources
– Whole grains, dried fruits, nuts, leafy
vegetables
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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
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Manganese
• Functions & mechanisms of action
– Transferases
– Hydrolases
– Lyases
– Oxido-reductases
– Ligases/synthetases
– Other roles
• Modulator of second messenger
pathways
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Manganese
• Interactions with other nutrients
– Iron; possibly calcium, zinc
• Excretion
– Mostly in bile
– Little in urine
– Sweat, skin desquamation
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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
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Manganese
• Assessment of nutriture
– Mononuclear blood cell/plasma/
serum/whole blood concentrations
– Enzyme activity
• Lymphocyte Mn-SOD
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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
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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
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Molybdenum
• Excretion
– Most as molybdate in urine
– Small amounts in bile, sweat, hair
• Recommended Dietary Allowance
– Adults: 45 µg
– Pregnancy/lactation: 50 µg
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Molybdenum
• Deficiency
– Diet rich in antagonistic substances
(e.g. sulfate, Cu, tungstate)
• Toxicity
– UL = 2 mg
• Assessment of nutriture
– No validated indicators
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Fluoride
• Sources
– Fluoridated water
– Some grains, some marine fish
– Tea
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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
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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
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Fluoride
• Interactions with other nutrients
– Aluminum, calcium, magnesium,
chloride
• Excretion
– Mostly in urine, also feces, sweat
• Adequate Intake
– Men: 4 mg; women: 3 mg
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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
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Perspective 12
Nutrient-Drug Interactions
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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
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Drug-Nutrient Interactions
• Effects of drugs on nutrient
absorption
• Effects of drugs on nutrient
metabolism
• Effects of drugs on nutrient
excretion
• Summary
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