Overview of Molybdenum in Biology

Current knowledge of the physiological effects of molybdenum, its environmental impact and its toxicology is surveyed with the object of assessing and defining both its essentiality as a trace metal and any hazards which may arise from the exposure of human beings and animals to molybdenum and its compounds. It is apparent from this survey that, although much is already known about physiological effects and toxicity of molybdenum, there are many aspects which require detailed study. Such studies have been and continue to be undertaken by the International Molybdenum Association.

Molybdenum an essential trace element

As a trace element molybdenum occurs in plants and animals in concentrations of a few parts per million. Molybdenum is an essential constituent of certain enzymes that catalyse redox reactions: in plants, reduction of molecular nitrogen and nitrate; in animals, oxidation (hydroxylation) of xanthine and other purines and aldehydes. Molybdenum is capable of forming complexes with many compounds of biological importance: carbohydrates, amino acids, flavins, porphyrins; but is probably taken up, transported, and excreted in animals as the simple molybdate ion, [MoO4]2-. Molybdenum is essential for plant growth because of its involvement in the processes of nitrogen fixation and nitrate reduction. For satisfactory plant growth, some soils that are deficient in molybdenum require supplemental molybdenum.

In some animals, an essential stage in the catabolism of purines is the oxidation of xanthine to uric acid, a reaction catalysed by the molybdenum-containing enzyme xanthine oxidase. At low molybdenum concentrations, the activity of xanthine oxidase is proportional to the molybdenum concentration; but at higher concentrations, molybdenum may have an inhibitory effect on the enzyme. In this and in other biological processes influenced by molybdenum there appears to be a threshold molybdenum concentration below which molybdenum may have a stimulating effect and above which the effect may be inhibitory.

In animals molybdenum also influences protein synthesis, and the metabolism of phosphorus, sulfur, potassium, iron, copper, zinc, and iodine. With some animals (chicks, red trout) added dietary molybdenum stimulates growth.
Sulfate and molybdate follow similar metabolic pathways. Sulfate will alleviate molybdenum toxicity. Molybdate and sulfate act together in creating copper deficiency in cattle and sheep giving rise to the teart condition. Molybdenum inhibits the activity of the enzyme liver sulfide oxidase and the toxicity of molybdenum compounds is enhanced by sulfide. In assessing possible biological effects of molybdenum it is important to take into account its metabolic interrelationships with other trace elements.

Reid, Scott D., MOLYBDENUM AND CHROMIUM, 2012, 375-415.
2 Homeostasis and Toxicology of Essential Metals

This 473-page book in English titled "Homeostasis and Toxicology of Essential Metals" contains 9 individually authored chapters. The book highlights a list of contributors and their respective institutions. Each chapter contains a list of references. Specific topics discussed include an introduction to metals in fish physiology and toxicology, chemical speciation, characterization, toxicity, essentiality, behavioral effects of metals such as copper, zinc, iron, nickel, cobalt, selenium, molybdenum and chromium, field studies on metal accumulation and effects in fish. This book will be of use to those interested in essential metals and toxicology of essential metals.

Homeostasis and Toxicology of Essential Metals, Homeostasis and Toxicology of Essential Metals, 2012, 31A

Molybdenum essential for life and less toxic than other heavy metals

The general conclusion is that molybdenum is essential for life and is much less toxic than many other metals of industrial importance. Molybdenum does not constitute a hazard to human beings either in trace concentrations occurring naturally or because of environmental pollution or in higher concentrations encountered in industrial processes and applications. Nevertheless molybdenum does have physiological effects and common sense precautions should be taken to avoid repeated exposure of human beings to concentrations of molybdenum compounds in excess of the WHO and other standards especially dusts and fumes of molybdenum metal and molybdenum trioxide powders.

Molybdenum not harmful

Exposure of animals and human beings to trace levels of molybdenum is unlikely to be harmful (except in those species in which the molybdenum-copper antagonism is important) and may indeed be beneficial in terms of increased growth. Exposure of human beings to molybdenum concentrations above the trace level may occur in mining and refining operations and in the chemical and metallurgical industries. No harmful effects of such exposure have been reported. The acute toxicity of molybdenum compounds has been assessed in studies with experimental animals. Molybdenum trioxide and water-soluble molybdates have slight toxicities in oral administration and inhalation of dusts; but insoluble molybdenum compounds, e.g., calcium, strontium and zinc molybdates and molybdenum disulfide, are completely nontoxic. Molybdate Orange, a pigment which contains molybdenum, lead and chromium, and Moly White, a pigment which contains zinc molybdate, are also nontoxic in animal experiments. The harmful effect of molybdenum-containing dusts on the lungs is enhanced by silica. Particular care should be taken in handling molybdenum hexacarbonyl and organomolybdenum compounds, and molybdenum pentachloride, where toxic effects are due to elements other than molybdenum which are present.

Acute molybdenum poisoning in human beings is extremely unlikely because of the massive dose required. The effect of repeated exposure to small concentrations of molybdenum compounds is more difficult to assess. In animals and human beings molybdenum is adsorbed and excreted rapidly and so is not likely to be a cumulative poison. In checking for possible molybdenum toxicity it is important to know where and in what form toxic effects may occur. In experimental animals molybdenum toxicity causes loss of weight, harmful changes in the liver, kidneys, and bones and diminution of the strength of conditioned reflexes.

Molybdenum and tungsten compared – redox potentials and biological role

The redox potentials of strictly analogous complexes of molybdenum and tungsten were studied using temperature dependent electrochemistry in order to evaluate a proposed influence of the potentials on the use of tungsten at thermophilic conditions and the use of molybdenum at mesophilic conditions in the molybdopterin dependent oxido reductases. Each pair of molybdenum and tungsten compounds was studied under identical conditions. The studies reveal that tungsten's redox potential is always more temperature sensitive than molybdenum's with a stronger shift of the potential upon temperature change in negative or positive direction depending on the ligand system.

The redox potential of tungsten is more temperature dependent than that of molybdenum for the redox transitions M(IV) / M(V) and M(V) / M(VI). An explanation is the more relativistic character of tungsten. With respect to the biological role of molybdenum and tungsten it can explain the preferred use of molybdenum wherever molybdenum is available and the evolutionary change from tungsten to molybdenum. Molybdenum is able to provide more stable conditions for redox processes with a smaller change of its redox potential upon temperature change and a smaller entropy gain or loss upon oxidation or reduction which is connected to a geometric change influencing the energies for substrate conversion and reorganisation.

Doring, A. and Schulzke, C., Tungsten's redox potential is more temperature sensitive than that of molybdenum, Dalton Transactions, 2010, 39, 5623-5629.

Trace element utilisation - review

Trace elements are used by all organisms and provide proteins with unique coordination and catalytic and electron transfer properties. Although many trace element-containing proteins are well characterized, little is known about the general trends in trace element utilization. We carried out comparative genomic analyses of copper, molybdenum, nickel, cobalt (in the form of vitamin B-12), and selenium (in the form of selenocysteine) in 747 sequenced organisms at the following levels: (i) transporters and transport-related proteins, (ii) cofactor biosynthesis traits, and (iii) trace element-dependent proteins. Few organisms were found to utilize all five trace elements, whereas many symbionts, parasites, and yeasts used only one or none of these elements. Investigation of metalloproteomes and selenoproteomes revealed examples of increased utilization of proteins that use copper in land plants, cobalt in Dehalococcoides and Dictyostelium, and selenium in fish and algae, whereas nematodes were found to have great diversity of copper transporters. These analyses also characterized trace element metabolism in common model organisms and suggested new model organisms for experimental studies of individual trace elements. Mismatches in the occurrence of user proteins and corresponding transport systems revealed deficiencies in our understanding of trace element biology. Biological interactions among some trace elements were observed; however, such links were limited, and trace elements generally had unique utilization patterns. Finally, environmental factors, such as oxygen requirement and habitat, correlated with the utilization of certain trace elements. These data provide insights into the general features of utilization and evolution of trace elements in the three domains of life.

Zhang, Y. and Gladyshev, V. N., General Trends in Trace Element Utilization Revealed by Comparative Genomic Analyses of Co, Cu, Mo, Ni, and Se, Journal of Biological Chemistry, 2010, 285, 3393-3405.

Biological trace elements database

Biological trace elements are required for biological processes and by all organisms. We describe a database, dbTEU (DataBase of Trace Element Utilization), that features known transporters and user proteins for five trace elements (copper, molybdenum, nickel, cobalt and selenium) and represents sequenced organisms from the three domains of life. The manually curated dbTEU currently includes approximaately 16 500 proteins from > 700 organisms, and offers interactive trace element, protein, organism and sequence search and browse tools.

Zhang, Y. and Gladyshev, V. N., dbTEU: a protein database of trace element utilization, Bioinformatics, 2010, 26, 700-702.