Molybdenum

Physiological Role
Distribution in Tissues
Absorption and Excretion
Homeostatic Control
Interactions with Other Elements
Requirements
Dietary Source
Deficiency
Mo Toxicity

I.  Physiological Role

  1. Mo is biologically active in a number of dependent enzymes. Mo5 + and Mo6 + are biologically most important since their reduction potential is appropriate for flavine interactions
    1. Xanthine oxidase acts on xanthines and purines to produce uric acid
      1. Purines may be converted to uric acid for excretion
      2. Purines may be directed into a "salvage pathway" for purine nucleotide biosynthesis
      3. Xanthine oxidase is found in animal tissues, ruminant milk, (See Emory, T. F. 1991. iron and your health. CRC Press), microorganisms
      4. Molecular weight 300,000, one mole contains 2 moles of Mo, 8 moles of Fe, and 2 moles of flavin adenine dinucleolide (FAD)
        1. Riboflavin reacting with fiavin adenine dinucleotide (FAD)
        2. FMN then reacts with ATP to produce FAD and Pi
      5. Xanthine dehydrogenase and xanthine oxide may be two interconvertible forms of the same enzyme (See Oxygen radicals and tissue injury, UpJohn Symposium 1988, p. 65)
    2. Aldehyde oxidase
      1. As the name implies, oxidizes RCHO and RCOOH. May be involved in detoxification of potentially harmful xenobiotics (see J. Nutr. 119:221. 1989)
      2. Found in animal tissues and microorganisms
      3. Deficiency of molybdenum cofactor, an organic Mo compound, impaired activities of xanthine dehydrogenase and sulfite oxidase (Clinical biochemistry 23:537. 1990)
    3. Sulfite oxidase catalyzes formation of SO4 from SO3
      1. Catalyzes formation of SO4 from SO3 to detoxify sulfite. This is the terminal step of sulfur amino acid metabolism
      2. Found in animal tissues
    4. Nitrate reductase
      1. Found in plants and microorganisms
      2. Reduces NO3- to NO2-
    5. Nitrogenase or molybdoferredoxin
      1. Found in plants and microorganisms
      2. Catalyzes formation of NH3 from N2
    6. As a component of the above enzymes, Molybdenum is required for growth, growth regulation(?) (Fed. Proc. 42:817, abst 3076, 1983), cellular oxidation, purine metabolism and is possibly involved in Fe metabolism

II.  Distribution in Tissues

  1. Blood levels of Mo vary sharply with intake
  2. Relative order of Mo concentrations in various tissues differ in sheep and cattle
  3. Tissue MO content increases with increasing MO intake
    1. In the normal dietary range (1-5 ppm Mo) differences in Mo concentrations in milk cannot be detected
    2. Mo content in milk responds directly to increases in Mo intake at higher levels

III.  Absorption and Excretion

  1. Mo absorption by swine is rapid and high (J. Nutr. 84:367, 1964)
    1. 80-90% is excreted in urine
    2. Fecal excretion is very low
  2. Mo absorption by ruminants is slow and much lower than for swine
    1. 2-10% is excreted in urine
    2. Fecal excretion may exceed 95%
    3. When the rumen is bypassed, the excretion pattern more nearly resembles that of swine
  3. Mo is absorbed from the gastric stomach, small intestine, and large intestine
    1. In ruminants, Mo is secreted into the rumen (J. Anim. Sci. 34:846, 1972)
    2. Although Mo is not absorbed from the rumen, its absorption lower in the digestive tract is reduced by passage through the rumen

IV.  Homeostatic Control

  1. Homeostatic control of Mo appears to be limited
    1. Blood Mo concentrations increase with intake
    2. Increases in Mo excretion with increasing intake are limited

V.  Interactions with Other Elements

  1. Cu-Mo-SO4 in ruminants has been discussed under copper
    1. The site of the Cu-Mo interaction appears to be the rumen
    2. Neither Cu nor Mo appear to be absorbed from the rumen, but formation of an insoluble complex there may inhibit absorption of both elements from the intestines
    3. When feed Mo is < 0.2 ppm, Cu toxicity is more likely
    4. When feed Mo is > 7 ppm, Cu deficiency may occur
      1. Cu-Mo antagonism can be circumvented when dietary Mo is high by parenteral administration of Cu
        1. Subcutaneous injection
        2. Continuous infusion
    5. High dietary levels of either sulfur or molybdenum may increase excretion of the other
    6. Sulfate and Mo may compete for sites on a common membrane transport system
    7. Mo can inhibit reduction of sulfate to sulfite
      1. Under some conditions, Mo may decrease the amount of sulfide formed in the rumen, thereby increasing Cu availability to the animals
      2. Conversely, inhibitory effect of Mo on sulfide production can be decreased by formation of a nonavailable complex of Mo with Cu
    8. Inorganic sulfate enhances the effect of Mo in limiting Cu-storage in the liver
  2. Zn and Mn may reduce availability of Mo in poultry diets
  3. Tungston is antagonistic to Mo

VI.  Requirements

  1. Poultry, approximately 5 ppm
    1. Corresponds to 0.15 ppm biologically available Mo
    2. Addition of 1-2 ppm Mo as Na molybdate is recommended in the event it is ever approved by FDA
    3. Pushing for maximum growth with diets containing high levels of protein, Cu, antibiotics, Mn and Zn may create a mineral imbalance of sorts with Mo being the first micro element to become limiting
  2. Swine - the requirement level has not been defined
  3. Cattle and Sheep - the requirement level has not been defined.

VII.  Dietary Sources

  1. Naturally growing herbage usually reflects Mo content of the soil
  2. Animal by product meals are usually poor sources of Mo since the liver and kidneys are usually not included
  3. Mo content of the soybean is largely unavailable to poultry

VIII.  Deficiency

  1. Poultry (pp. 43-44 in 1978 Ga. Nutr. Conf.)
    1. Suspected when a response to addition of Mo in the diet is seen:
      1. Improved growth
      2. Increased xanthine dehydrogenase activity in liver and intestine
    2. Chicks responded to supplemental Mo when fed a Iow Zn diet containing isolated soy protein
      1. No response when the diet contained vitamin-free casein as the protein source
      2. No response when a soy protein diet contained high Zn
    3. Mo supplementation of breeding stock has improved fertility and hatchability of eggs
    4. Pseudo clubbed down in breeders characterized by poor hatchability and weak chicks with classical symptoms of riboflavin deficiency-which do not respond to extra riboflavin.
      1. Both riboflavin and Mo are essential components of several enzymes, notably, xanthine oxidase (mol. wt. 300,000; contains 2 moles of flavine adenine dinucleotide, 2 moles of Mo, and 8 moles of Fe per mole)
  2. Rats - Mo deficiency cannot be induced simply by omitting Mo from purified diets
    1. Tungsten, a competitive antagonist of Mo in vivo, prevents the uptake and utilization of Mo. (J. Nutr. 114:1652. 1984)
    2. Mo deficiency results in accumulation of Fe in the liver
      1. Fe accumulation seen in Mo-deficient animals only when adequate Fe (24 ppm) was fed
      2. No accumulation of Fe was detected in rats fed diets with 6 or 12 ppm Fe
    3. Accumulation of Fe was seen only with virtually complete inhibition of xanthine oxidase activity
      1. Inhibition of xanthine oxidase by only 60% did not cause accumulation, of Fe in the liver
    4. Ruminants - Mo might be considered as deficient if it is so low that Cu toxicity results

IX.  Mo Toxicity

  1. Relative tolerance to Mo is cattle (50-100 ppm) < sheep < poultry (200-500 ppm) rodents < horses < swine (1,000 ppm) = humans
    1. Cattle are more tolerant to inorganic Mo (up to 50 ppm) than to Mo found in vegetation (5 ppm when Cu is low)
    2. The major symptoms of chronic Mo toxicity in ruminants are those of Cu deficiency with diarrhea being especially prominent
    3. Occurrence of severe acute Mo poisoning can be practically excluded due to refusal of poisoned feed
    4. Contrasting responses of ruminants and nonruminants to Mo-Cu antagonism are probably related to the influence of the rumen
    5. Molybdenosis is a potential problem in ruminants grazing on coal mine spoils (J. Range Management 31:34. 1978)




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