Molybdenum (Mo) - General Discussion

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.