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Updated: Mar 8 2019

Trace Metals

  • Overview
    • Definition
      • micronutrients required in the diet for necessary cellular functions
    • Major examples
      • iron (Fe)
      • copper (Cu)
      • zinc (Zn)
      • chromium (Cr)
      • fluoride (F)
      • iodide (I)
      • selenium (Se)
    • Others
      • V, Mo, Mn, Co, and Ni
    • Function
      • part of metalloenzyme
        • enzyme has no activity without the metal
        • metal is fixed
        • metal:protein is constant
        • example
          • carbonic anhydrase
      • part of metal-containing enzyme
        • enzyme may have activity without the metal
        • metal is reversibly bound
        • metal:protein ratio is variable
        • example
          • glycogen phosphorylase kinase
    • Oxidative stress
      • organometallic side reactions that damage tissue
        • many metals undergo the Fenton reaction in vivo
          • oxidation of metal and donation of an electron to oxygen
          • most common metals that undergo reaction are Fe2+ and Cu+
          • creation of hydroxyl radicals
        • heme iron can generate superoxide radicals (O2*)
      • reactions happen frequently, but the body can defend itself with anti-oxidants
        • oxidative stress occurs when pro-oxidants > anti-oxidants.
      • examples of oxidative stress damage
        • stroke
        • Parkinson’s
        • Alzheimer’s
  • Iron
    • Source
      • diet
      • recycled from destroyed erythrocytes
    • Forms
      • ferrous iron (Fe2+)
        • dangerous
        • causes oxidative stress
        • found in hemoglobin
      • ferric iron (Fe3+)
        • less dangerous
        • methemoglobinemia (metHb) occurs when Fe3+ is found in hemoglobin
    • Absorption
      • Fe-containing compounds are solubilized in low stomach pH
      • Fe3+ is reduced to Fe2+ (requires vitamin C) in intestine so it can cross gut lumen
      • ferroportin brings Fe3+ into bloodstream from enterocytes
        • mediates amount of Fe released into the blood
        • hepcidin inhibits ferroportin
          • antibacterial because it lowers the availability of iron in the plasma
    • Storage
      • must be immediately used or stored to prevent:
        • bacterial utilization
          • Fe required for growth
        • formation of iron oxides
        • free radicals (Fe + O2)
      • site
        • hepatocytes (main)
        • enterocytes
        • macrophages
      • stored as ferritin (Fe3+)
      • hemosiderin binds excess Fe3+ to prevent from entering the blood
    • Transport
      • carried as Fe3+ by transferrin in the blood
        • transferrin chelates the Fe3+ and transports it in the blood to tissues.
          • maintains solubility and keeps unreactive
          • transferrin receptors on cells endocytose transferrin:Fe complex
          • Fe3+ released into cell triggered by low pH
          • transferrin returns to cell surface to be used again
      • ferroxidase (aka ceruloplasmin) oxidizes Fe2+ to Fe3+ for transport and storage
        • ferritin can also oxidize Fe for storage
    • Excretion
      • no cellular mechanism for iron excretion
      • lost from blood loss and removal of skin cells and other epithelial cells
    • Toxicity
      • beyond the sequestration capacity of ferritin
      • causes oxidative stress
    • Disorders in iron handling
      • hereditary hemochromacytosis
  • Copper
    • Role
      • human metabolism
      • like other metals, free copper is potentially toxic by donating electrons
        • creates hydroxyl radicals and other reactive oxygen species
      • copper is a cofactor for many metalloproteins
        • examples
          • lysyl oxidase (collagen synthesis)
          • tyrosinase (melanin synthesis)
    • Transport
      • albumin and ceruloplasmin carry copper in the blood
        • similar role to transferrin in iron transport
      • metallothionein is a carrier of copper, zinc, and many other metals
        • role in preventing oxidative stress in the cell
        • thiol groups from many cysteine residues mediate binding
    • Excretion
      • excess copper removed in the bile
        • unlike iron with no mechanism of excretion
    • Deficiency
      • causes
        • excess zinc
          • metallothionein carries both copper and zinc
          • copper is displaced when zinc concentrations rise
      • symptoms
        • a function of what enzymes require copper
          • ferroxidase
            • catalyzes oxidation of iron from Fe2+ to Fe3+
            • result is microcytic anemia
          • lysyl oxidase
            • crosslinks collagen fibers
            • result is poor wound healing
            • aortic dissection
    • Disorders in copper handling
      • Wilson's disease
      • Menke’s disease
        • X-linked gene mutation in ATP7A
          • ATP-dependent copper efflux protein
        • aka Ehlers-Danlos syndrome type IX
        • inability of enterocytes to release absorbed copper
        • copper at toxic levels in small intestine and kidneys
        • copper in circulation and in brain at low levels
        • symptoms
          • presents like a copper deficiency
          • seizures, failure to thrive, and neurodegeneration
          • steel-colored and brittle hair
            • due to role of copper in metalloprotein lysyl oxidase which crosslinks collagen for added strength
            • at low serum concentrations of copper, this enzyme cannot function
  • Zinc
    • Function
      • hundreds of enzymes require zinc
        • important examples
          • carbonic anhydrase
          • ACE (angiotensin I converting enzyme)
          • RNA and DNA polymerase
    • Transport
      • metallothionein carries zinc
        • competes with copper
    • Deficiency
      • causes
        • poor diet
        • alcoholism
          • liver unable to handle zinc properly
      • symptoms
        • impaired collagenase
          • delayed wound healing
        • impaired zinc finger transcription factor motifs
          • hypogonadism
            • ↓ adult hair (axillary, facial, and pubic)
        • ↓ in senses
          • dysgeusia (lack of taste)
          • anosmia (lack of smell)
        • diarrhea
        • hair loss (alopecia)
  • Chromium
    • Deficiency
      • causes
        • total parenteral nutrition (TPN)
      • symptoms
        • a function of what proteins/enzymes require chromium
          • hypothesized to play a role as part of glucose tolerance factor
            • ↓ glucose tolerance
  • Flouride
    • Source
      • mainly fluoridated water
    • Deficiency
      • plays a role in bone and teeth formation/strength
        • ↑ bone fractures
        • dental caries
  • Iodine
    • Source
      • mainly iodized salt
    • Deficiency
      • plays a role in synthesis of thyroid hormone
        • goiter
        • ↓ thyroid hormone output
  • Selenium
    • Deficiency
      • causes
        • total parenteral nutrition (TPN)
      • symptoms
        • plays a role in glutathione peroxidase that protects against oxidative stress
          • damage to tissues with high metabolic activity
            • muscle pain
            • cardiomyopathy
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