MOLYBDENUM

Molybdenum, an essential trace element for microorganisms, plants and animals, was discovered in 1778 by a Swedish chemist named Karl Scheele. Molybdenum, which was originally confused with lead, took its name from the Greek word molybdos, meaning lead-like. With the discovery of the first molybdenum-containing enzymes in the 1950s, the importance of molybdenum began to be understood. Untill now, only four enzymes that require molybdenum have been identified in humans:

 

Sulfite oxidase: Sulfite oxidase, an enzyme found in mitochondria, catalyzes the conversion of sulfite to sulfate, a reaction essential for the metabolism of sulfur-containing amino acids (methionine and cysteine).

 

Xanthine oxidase: Converts hypoxanthine to xanthine and also catalyzes the breakdown of nucleotides (DNA and RNA precursors) to form uric acid, converting xanthine into uric acid, which contributes to the plasma antioxidant capacity of the blood.

 

Aldehyde oxidase: Aldehyde oxidase is abundant in the liver and is an important enzyme in phase 1 drug metabolism.

 

Mitochondrial amidoxime-reducing component (mARC): Its physiological significance is still unclear.

 

Food Sources Containing Molybdenum

Beans are among the richest sources of molybdenum. Lima beans, especially small white beans, red beans, green beans, kidney beans and peas are also rich in molybdenum. Grains such as wheat, oats and rice can also be good sources of molybdenum. Some vegetables such as asparagus, some dark leafy vegetables, and some Brassica vegetables also contain significant amounts of molybdenum.

Molybdenum content in soil varies and can lead to a wide range of molybdenum content for a given food, depending on where the crop is grown. Although having lower molybdenum concentrations than other food sources, milk and cheese products provide the majority of dietary molybdenum in youth, accounting for 27-40% of intake due to amount consumed. For adults, grain products are the primary source of dietary molybdenum, accounting for 19-20% of intake.

 

Wilson's Disease Treatment and Molybdenum

In humans, tetrathiomolybdate therapy has been developed for Wilson's disease, a genetic disease in which copper accumulation in tissues leads to liver and brain damage. In Wilson disease, copper that does not bind to ceruloplasmin circulates and accumulates in tissues, causing liver damage, neurological complications, and brain damage. As tetrathiomolybdate, molybdenum can form a strong complex with copper and protein. Tetrathiomolybdate given with food prevents copper absorption by forming a complex with copper and protein in the diet. Tetrathiomolybdate given without food is absorbed into the bloodstream and forms complexes with circulating copper and albumin, preventing copper from accumulating in cells and causing toxicity.

 

Toxicity

Molybdenum can be very toxic to some animals, especially cattle and sheep, because high molybdenum intake causes secondary copper deficiency in these animals. The interaction of molybdenum with sulfur results in the formation of thiomolybdates. Tetrathiomolybdate, a thiomolybdate with four sulfur atoms, can form complexes with copper, preventing its absorption and blocking the activity of copper-dependent enzymes.

However, the potential for molybdenum toxicity in humans is low. However, acute toxicity was reported in a case study where molybdenum supplements were taken at 300-800 µg per day for an 18-day period, resulting in hallucinations and seizures.

 

Hereditary Molybdenum Cofactor Deficiency

In each of the molybdenum enzymes, activity is catalyzed through a tricyclic cofactor called molybdenum cofactor (MoCo), consisting of a pterin, a dithiolene, and a pyran ring. Since molybdenum functions only in the Moco form in humans, any disturbance in Moco metabolism can disrupt the function of all molybdoenzymes. Moco is synthesized de novo through a multistep metabolic pathway involving four genes: MOCS1, MOCS2, MOCS3, and GPHN. More than 60 mutations have been identified to date, mostly affecting MOCS1 and MOCS2.

The absence of a functional Moco has a direct effect on the activity of molybdoenzymes. In the absence of sulfite oxidase activity, sulfite, taurine, S-sulfocysteine and thiosulfate accumulate. This metabolic profile is also seen in isolated sulfite oxidase deficiency (ISOD), an inherited condition caused by mutations in the SUOX gene, which encodes sulfite oxidase. Moco deficiency (MocoD) also affects the xanthine pathway, leading to hypoxanthine and xanthine accumulation and low or undetectable uric acid concentrations in the blood. MocoD and ISOD have been diagnosed in more than 100 people worldwide.

Mutations in the molybdenum cofactor biosynthetic pathway lead to combined deficiency of all molybdenum-dependent enzymes. Molybdenum cofactor deficiency Type A is caused by mutations in the MOCS1 gene, while Type B deficiency is caused by mutations in the MOCS2 gene. Both Type A and Type B deficiencies result in loss of sulfite oxidase activity, which is also observed in isolated sulfite oxidase deficiency and is characterized by severe neurological abnormalities in affected patients.

 

Recommended Dietary Allowance (RDA)

Table 1. Recommended Dietary Allowance (RDA) for Molybdenum
Life Stage	Age	Males (µg/day)	Females (µg/day)
Infants	0-6 months	2(AI)	2(AI)
Infants	7-12 months	3(AI)	3(AI)
Children	1-3 years	17	17
Children	4-8 years	22	22
Children	9-13 years	34	34
Adolescents	14-18 years	43	43
Adults	19 years and older	45	45
Pregnancy	all ages	-	50
Breast-feeding	all ages	-	50

 

Table 2. Tolerable Upper Intake Level (UL) for Molybdenum
Age Group	UL (µg/day)
Infants 0-12 months	Not possible to establish*
Children 1-3 years	300
Children 4-8 years	600
Children 9-13 years	1,100 (1.1 mg/day)
Adolescents 14-18 years	1,700 (1.7 mg/day)
Adults 19 years and older	2,000 (2.0 mg/day)
*Source of intake should be from food and formula only.

 

Older adults (>50 years): Because aging is not associated with significant changes in molybdenum requirements, the recommendation for older adults is the same as for adults 50 years of age and younger.

 

Supplements

Molybdenum in single-nutrient and multi-nutrient supplements comes in various forms, including sodium molybdate, ammonium molybdate, molybdenum citrate, molybdenum chloride, and molybdenum glycinate, among others.

 

REFERENCES

Novotny, J. A., & Peterson, C. A. (2018). molybdenum Advances in Nutrition, 9(3), 272-273. https://doi.org/10.1093/advances/nmx001

https://lpi.oregonstate.edu/mic/minerals/molybdenum#nutrient-interactions