| Molybdenum is essential to all organisms as a constituent of
numerous metalloenzymes. Molybdenum is known to be an integral part
of no less than three essential enzymes:
1- Xanthine oxidase
2- Aldehyde oxidase
3- Sulfite oxidase
The average American daily intake in food ranges from 76 to 109
mcg per day - the RDA for Mo is 250 mcg per day.
Toxicity occurs at 10 mg per day as a gout-like disease and
interference with copper metabolism.
Molybdenum is a trace mineral nutrient present in all body
tissues. Only minute amounts of this mineral are required for
health. Molybdenum possibly helps to retard degenerative diseases,
cancer and aging. A molybdenum-containing enzyme of the liver
(sulfite oxidase) destroys sulfite, used as a preservative in foods
and drugs. In this role molybdenum acts as a detoxification agent.
The production of uric acid from the degradation of purines
(building blocks of RNA and DNA) requires molybdenum.
A Recommended Dietary Allowance (RDA) has not been determined for
molybdenum, and the requirement for optimal health is not known. A
safe and adequate daily intake for adults is estimated to be 75 to
250 mcg. People who rely on a diet of refined and processed foods,
who have high levels of uric acid and are prone to gout-like
symptoms, or who are copper deficient can potentially be deficient
in this trace mineral. High copper intake antagonizes molybdenum
uptake; very high levels of molybdenum increase copper losses.
Molybdenum - Biochemical function
Aspects of the biochemistry and
biological significance of molybdenum have been reviewed elsewhere.
In plants and lower organisms, molybdenum dependent enzymes are
involved in nitrogen fixation, in the conversion of nitrate to
ammonia and in a series of other oxidation-reduction reactions. The
three principal molybdenum-containing enzymes of human and animal
tissues, namely xanthine dehydrogenase/oxidase, aldehyde oxidase and
sulfite oxidase share a common cofactor, molybdopterin, a
substituted pterin to which molybdenum is bound by two sulfur atoms.
Discovery of molybdenum in the enzyme xanthine dehydrogenase/oxidase
involved in the conversion of tissue purines to uric acid provided
the first evidence of the essentiality of this element. Normally the
enzyme acts as a dehydrogenase but, when reacting with oxygen, it
initiates the production of a series of highly reactive oxygen-rich
free radicals believed to be responsible for some features of tissue
damage induced by physical injury and a wide variety of toxins,
including excess molybdenum.
A reduced tissue activity of this enzyme has been associated with
xanthinuria, a genetic defect characterized by a low output of uric
acid and high concentrations of xanthine and hypoxanthine in blood
and urine. Clinical manifestations become apparent only after renal
calculi have formed or after deposition of xanthine and hypoxanthine
in muscles has resulted in a mild myopathy.
Low molybdenum intakes also reduce tissue xanthine dehydrogenase
activity, but there is no convincing evidence that changes in
molybdenum intake from conventional diets sufficiently influence
enzyme activity to cause clinical changes in mammals. Furthermore,
while a low xanthine dehydrogenase activity in tissues or changes in
its substrate/product relationships (e.g. of the xanthine +
hypoxanthine/uric acid ratio in plasma) may reflect a low molybdenum
status, such responses are insufficiently specific to be of
diagnostic value. Thus xanthine dehydrogenase activity also
decreases if protein intake is low and in cases of hepatoma.
Conversely, activity increases if protein intake is high, if vitamin
E status is low, or if interferon or agents stimulating its release
are given. Claims that high intakes of molybdenum stimulate tissue
xanthine dehydrogenase activity await verification. The
molybdenoenzyme aldehyde oxidase is structurally and chemically
similar to xanthine oxidase exhibits a similar distribution between
tissues and shares some substrates. However, other biochemical
properties differ and its principal metabolic roles are not known.
An additional molybdenoenzyme, sulfite oxidase, responsible for
the conversion of sulfite derived from cysteine, methionine and
related compounds into inorganic sulfate, has been isolated from the
liver of humans and other species. Instances of genetic "deficiency"
of sulfite oxidase have been detected in early human infancy and
have a lethal outcome at the age of 2-3 years. The lesion results in
severe neurological abnormalities, mental retardation and ectopy of
the lens. Urinary outputs of sulfite, thiosulfate and S-sulfo-L-cysteine
all increase and urinary sulfate decreases. These pathological
changes may result either from the accumulation of toxic
concentrations of sulfite in some critical organs or from inadequate
production of the sulfate required for synthesis of sulfolipids,
proteins and sulfate-conjugates. Other inborn metabolic disorders
are associated with genetically related deficiencies of aldehyde
oxidase, xanthine oxidase and sulfite oxidase caused by failure to
synthesize their molybdopterin cofactor.
Molybdenum Deficiency
A nutritional deficiency of molybdenum
giving rise to clinical symptoms suggestive of a deficiency of
sulfite oxidase has been reported by Abumrad et al. in a human
patient subjected to prolonged total parenteral nutrition. The
clinical symptoms included irritability leading to coma,
tachycardia, tachypnea and night blindness. A reduced intake of
protein and sulfur-containing amino acids alleviated the symptoms,
whereas they were exacerbated by infusion of sulfite. Tissue sulfite
oxidase activity was low; thiosulfate excretion increased 25-fold,
sulfate output declined by 70% and plasma methionine increased
markedly. The clinical symptoms of molybdenum deficiency were
totally eliminated by supplementation with 300 mcg of ammonium
molybdate (147 mcg of molybdenum) daily. Further evidence of the
essentiality of molybdenum came from a study of two young adults
with Crohn disease maintained on total parenteral nutrition after
ileal resection. Both had extensive losses of trace minerals
including molybdenum (350-530 Mg of molybdenum/day) from the
intestinal tract. Parenteral infusion of 500 mcg of ammonium
molybdate (225 mcg of molybdenum) increased uric acid levels in the
plasma and urine of these patients.
It has been claimed that molybdenum status influences
susceptibility to certain forms of cancer and that the high
incidence of esophageal cancer among the Bantu in Transkei (South
Africa) is associated with a deficiency of this element in locally
available food. Studies in Henan province, China, suggest that a
high incidence of esophageal cancer is associated with lower than
normal contents of molybdenum in drinking water and food as well as
in serum, hair and urine. Esophageal cancer tissue also had lower
molybdenum content than normal. It may well be relevant that
inclusion of 2 or 20 mcg of molybdenum/g in the diet of rats has
been found to inhibit esophageal and stomach cancer following the
administration of N-nitrososarcosine ethyl ester. Molybdenum in the
drinking water of rats at a concentration of 10 mg/l inhibited
mammary carcinogenesis induced by N-nitroso-N-methylurea.
Molybdenum Requirements
In 1973, a WHO Expert Committee suggested
that 2 mcg of molybdenum per kg of body weight per day
would be adequate to maintain normal health. |
