Microminerals

1
Chapter 12

• Microminerals

2
Introduction

• Precise definition of essential micromineral
  not established
• Sometimes defined as mineral needed in amounts of
  lt100 mg/day
• RDAs established for 6
• AIs for 3 others

3
Iron

• Sources
• Heme iron meat, fish, poultry
• Nonheme iron nuts, fruits, vegetables, grains,
  tofu, dairy
• Grain foods fortified with iron

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

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

6
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
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
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
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
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
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
Iron

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

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

14
Iron

• Recommended Dietary Allowance
• Men 8 mg
• Women premenopausal 18 mg, postmenopausal 8 mg
• Pregnancy 27 mg lactation 9 mg

15
Iron

• Deficiency iron deficiency with without anemia
• Vulnerable
• Infants/young children
• Adolescents
• Menstruating females
• Pregnant women
• Supplements

16
Iron

• Toxicity hemochromatosis
• Mutations in HFE gene
• Body cannot accurately sense iron stores and
  down-regulate intestinal absorption

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

18
Zinc

• Sources
• Red meats, seafood, poultry, pork, dairy
• Whole grains, vegetables
• Availability affected by heat, Maillard reaction
  products
• Recycled from pancreatic biliary secretions

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

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

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

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

23
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
Zinc

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

25
Zinc

• Interactions with other nutrients
• Vitamin A
• Copper
• Calcium
• Cadmium
• Excretion
• Mostly through GI tract
• Small amount in urine through skin
  exfoliation/sweat

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

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

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

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

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

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

32
Copper

• Storage
• Concentrates in liver, brain kidneys
• Stored bound to amino acids, proteins,
  chaperones
• Metallothionein - stores up to 12 Cu atoms

33
Copper

• Functions mechanisms of action
• Ceruloplasmin
• Superoxide dismutase
• Cytochrome c oxidase
• Amine oxidases
• Tyrosine metabolism--dopamin monooxygenase
  p-hydroxyphenylpyruvate hydroxylase

34
Copper

• Lysyl oxidase
• Peptidylglycine alpha-amidating monooxygenase
• Other roles
• Angiogenesis
• Immune system function
• Nervy myelination
• Endorphin action
• Pro-oxidant
• Influences gene expression

35
Copper

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

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

37
Copper

• Deficiency
• Excessive zinc consumption, nephrosis, GI
  malabsorption
• Toxicity
• UL 10 mg
• Wilsons disease
• Supplements

38
Copper

• Assessment of nutriture
• Serum/plasma/RBC Cu
• Serum ceruloplasmin
• Response of serum ceruloplasmin to Cu supplements
• Cu concentrations in hair not useful

39
Selenium

• Sources
• Plant content variable based on soil
• Seafood
• Absorption, transport, uptake, storage,
  metabolism
• Absorption
• Selenoamino acid absorption
• Factors influencing selenium absorption

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

41
Selenium

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

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

43
Selenium

• Interactions with other nutrients
• Iron copper
• Methionine intake
• Excretion
• About equally in urine feces
• Lungs skin
• Exhalation of dimethylselenide

44
Selenium

• Recommended Dietary Allowance
• Adults 55 µg
• Pregnancy 60 µg lactation 70 µg
• Deficiency
• Keshan disease
• Kashin-Becks disease
• People on total parenteral nutrition

45
Selenium

• Toxicity
• UL 400 µg
• Assessment of nutriture
• Blood plasma concentrations
• Activities concentrations of selenoproteins
• SEL P, glutathione peroxidase
• Toenails, urinary concentration

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

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

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

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

50
Chromium

• Excretion
• Mostly in urine, also desquamation of skin cells
• Adequate Intake
• Adults 50 or lt
• Men 35 µg women 25 µg
• Adults gt50
• Men 30 µg women 20 µg
• Pregnancy 30 µg lactation 45 µg

51
Chromium

• Deficiency
• TPN, severe trauma stress
• Supplements
• Toxicity
• Assessment of nutriture
• No specific tests
• Observation of effects of Cr supplementation

52
Iodine

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

53
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
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

55
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
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
Iodine

• Toxicity
• UL 1,100 µg
• Assessment of nutriture
• Urinary excretion
• Thyroid size
• Radioactive iodide (131I) uptake
• Serum TSH concentrations

58
Manganese

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

59
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

60
Manganese

• Functions mechanisms of action
• Transferases
• Hydrolases
• Lyases
• Oxido-reductases
• Ligases/synthetases
• Other roles
• Modulator of second messenger pathways

61
Manganese

• Interactions with other nutrients
• Iron possibly calcium, zinc
• Excretion
• Mostly in bile
• Little in urine
• Sweat, skin desquamation

62
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
Manganese

• Assessment of nutriture
• Mononuclear blood cell/plasma/ serum/whole blood
  concentrations
• Enzyme activity
• Lymphocyte Mn-SOD

64
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

65
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
Molybdenum

• Excretion
• Most as molybdate in urine
• Small amounts in bile, sweat, hair
• Recommended Dietary Allowance
• Adults 45 µg
• Pregnancy/lactation 50 µg

67
Molybdenum

• Deficiency
• Diet rich in antagonistic substances (e.g.
  sulfate, Cu, tungstate)
• Toxicity
• UL 2 mg
• Assessment of nutriture
• No validated indicators

68
Fluoride

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

69
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
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
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
Fluoride

• Deficiency
• Toxicity
• Fluorosis
• UL 1.3 mg for children 1-3
• 10 mg for children gt8 adults
• Assessment of nutriture
• Plasma or urine concentrations
• Ion-specific electrode potentiometry

73
Perspective 12

• Nutrient-Drug Interactions

74
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
Drug-Nutrient Interactions

• Effects of drugs on nutrient absorption
• Effects of drugs on nutrient metabolism
• Effects of drugs on nutrient excretion
• Summary