Plasma molybdenum reflects dietary molybdenum intake

The relationship between plasma molybdenum (Mo) and dietary intake has not been investigated in humans. We developed an isotope dilution method to determine molybdenum in 0.5 mL blood plasma by ICP-MS and conducted a study to determine the effect of dietary intake on plasma molybdenum. Twelve young men consumed a very low Mo diet (22 microg/day) for 24 days while confined to the WHNRC metabolic research unit and plasma molybdenum was monitored. (97)Mo was infused in four of the subjects (Group 1) to follow its clearance from the blood. The other eight remained in unit for 120 days (an additional 96 days). Four consumed the 22 microg/day molybdenum diet for 102 days followed by 467 microg/day for 18 days (Group 2). and four consumed five levels of dietary molybdenum for 24 days each (Group 3). (100)Mo was added to the diet one or more times at each dietary level. Total plasma molybdenum and (100)Mo were monitored throughout the study. Plasma molybdenum in the 12 subjects decreased from 8.2 +/- 0.5 to 6.1 +/- 0.5 nmol/L after 13 days of low molybdenum intake and was 5.1 +/- 0.5 nmol/L after 24 days. In Group 2, average plasma molybdenum was 7.8 +/- 0.9 nmol/L at the beginning of the study, 5.4 +/- 0.4 nmol/L during the 102 days low molybdenum period, and 16.5 +/- 0.6 nmol/L during the high molybdenum period. Plasma molybdenum in Group 3 was 4.2 +/- 2.1 nmol/L at 22 microg/day; 5.8 +/- 2.5 nmol/L at 72 microg/day; 6.6 +/- 2.3 nmol/L at 121 microg/day; 19.7 nmol/L +/-2.1 at 467 microg/day; and 43.9 +/- 2.1 nmol/L at 1490 microg/day. The results demonstrate that, in contrast to most other essential minerals, plasma molybdenum reflects low and high dietary molybdenum intakes within 14 days and may a useful indicator of low and high dietary intakes.     

Bacterial reduction of hexavalent molybdenum to molybdenum blue

A bacterium that was able to tolerate and reduce as high as 50 mM of sodium molybdate to molybdenum blue has been isolated from a metal recycling ground. The isolate was tentatively identified as Serratia sp. strain Dr.Y8 based on the carbon utilization profiles using Biolog GN plates and partial 16S rDNA molecular phylogeny. ANOVA analysis showed that isolate Dr.Y8 produced significantly higher (P < 0.05) amount of Mo-blue with 3, 5.1 and 11.3 times more molybdenum blue than previously isolated molybdenum reducers such as Serratia marcescens strain Dr.Y6, E. coli K12 and E. cloacae strain 48, respectively. Its molybdate reduction characteristics were studied in this work. Electron donor sources such as sucrose, mannitol, fructose, glucose and starch supported molybdate reduction. The optimum phosphate, pH and temperature that supported molybdate reduction were 5 mM, pH 6.0 and 37°C, respectively. The molybdenum blue produced from cellular reduction exhibited a unique absorption spectrum with a maximum peak at 865 nm and a shoulder at 700 nm. Metal ions such as chromium, silver, copper and mercury resulted in approximately 61, 57, 80, and 69% inhibition of the molybdenum-reducing activity at 1 mM, respectively. The reduction characteristics of strain Dr.Y8 suggest that it would be useful in future molybdenum bioremediation.     

Nitrogenases without molybdenum

For 50 years molybdenum had been considered to have an indispensable catalytic function for nitrogen fixation. Two nitrogenases recently isolated from the bacterium Azotobacter have changed this view. One is a vanadium-containing enzyme and the other lacks both molybdenum and vanadium. Similar nitrogenases may occur in other nitrogen-fixing organisms.     

Cell biology of molybdenum

The transition element molybdenum (Mo) is of essential importance for (nearly) all biological systems as it is required by enzymes catalyzing diverse key reactions in the global carbon, sulfur and nitrogen metabolism. The metal itself is biologically inactive unless it is complexed by a special cofactor. With the exception of bacterial nitrogenase, where Mo is a constituent of the FeMo-cofactor, Mo is bound to a pterin, thus forming the molybdenum cofactor (Moco) which is the active compound at the catalytic site of all other Mo-enzymes. In eukaryotes, the most prominent Mo-enzymes are (1) sulfite oxidase, which catalyzes the final step in the degradation of sulfur-containing amino acids and is involved in detoxifying excess sulfite, (2) xanthine dehydrogenase, which is involved in purine catabolism and reactive oxygen production, (3) aldehyde oxidase, which oxidizes a variety of aldehydes and is essential for the biosynthesis of the phytohormone abscisic acid, and in autotrophic organisms also (4) nitrate reductase, which catalyzes the key step in inorganic nitrogen assimilation. All Mo-enzymes, except plant sulfite oxidase, need at least one more redox active center, many of them involving iron in electron transfer. The biosynthesis of Moco involves the complex interaction of six proteins and is a process of four steps, which also includes iron as well as copper in an indispensable way. Moco as released after synthesis is likely to be distributed to the apoproteins of Mo-enzymes by putative Moco-carrier proteins. Xanthine dehydrogenase and aldehyde oxidase, but not sulfite oxidase and nitrate reductase, require the post-translational sulfuration of their Mo-site for becoming active. This final maturation step is catalyzed by a Moco-sulfurase enzyme, which mobilizes sulfur from l-cysteine in a pyridoxal phosphate-dependent manner as typical for cysteine desulfurases.     

Effect of molybdenum supplementation onN-nitroso-N-methylurea-induced mammary carcinogenesis and molybdenum excretion in rats

Molybdenum (Mo) supplementation reduces the incidence of nitrosamine-induced tumors in the esophagus and forestomach of laboratory animals, and the incidence of mammary cancer in female rats induced byN-nitroso-N-methylurea (NMU). The present study was conducted to evaluate the effect of graded amounts of Mo on NMU-induced mammary carcinogenesis, and on the excretion of Mo and copper (Cu). Female Sprague-Dawley rats aged 5 wk were givenad libitum a low-Mo (0.026 mg/kg) diet and deionized water. After 15 d, a single SC injection of 50 mg NMU/kg body wt was administered to each of 30 rats in groups 2–5. Eight rats in group 1 served as untreated control. One week after the carcinogen treatment, 0.1, 1.0, or 10 mg Mo from sodium molybdate were added to each liter of drinking water for groups 3, 4, and 5, respectively. Groups 1 and 2 did not receive any Mo supplementation. After the rats had been Mosupplemented for 38, 67, and 85 d, 48-h urine and fecal samples were collected from the same 48 rats, and Mo and Cu were determined. Molybdenum seemed to have little effect on Cu excretion. At each time interval, animals fed 0 or 0.1 mg Mo/L excreted more Mo in feces than in urine, whereas rats fed 1 and 10 mg Mo/L water excreted more Mo in urine than in feces, which indicates that Mo absorption was not easily saturated as the amount of Mo increased. However, the liver became saturated with Mo when 0.1–1 mg Mo/L was fed. The total number of palpable tumors per group 101 d after NMU administration was 109, 115, 101, and 81, and the total carcinomas per group were 92, 96, 86, and 65 for the animals in groups 2–5, respectively. The results indicate that supplemental Mo in the amount of 10 mg/L of drinking water inhibited mammary carcinogenesis.     

Polyoxoalkoxy molybdenum and vanadium clusters

While the chemistry of polyoxoanions has been extensively studied, the related polyoxoalkoxide clusters remain relatively unexplored. Recent investigations into the coordination chemistry of polyoxoanions with alkoxide ligands demonstrate the existence of a rich structural chemistry which is now emerging. The introduction of alkoxide ligands into polyoxoanion cores significantly expands the structural diversity of the cluster types and allows the isolation not only of fully-oxidized cores with all metal centers possessing d⁰ electronic configurations but of fully-reduced and mixed valence systems.     

Biology of the molybdenum cofactor

The transition element molybdenum (Mo) is an essential micronutrient for plants where it is needed as a catalytically active metal during enzyme catalysis. Four plant enzymes depend on molybdenum: nitrate reductase, sulphite oxidase, xanthine dehydrogenase, and aldehyde oxidase. However, in order to gain biological activity and fulfil its function in enzymes, molybdenum has to be complexed by a pterin compound thus forming the molybdenum cofactor. In this article, the path of molybdenum from its uptake into the cell, via formation of the molybdenum cofactor and its storage, to the final modification of the molybdenum cofactor and its insertion into apo-metalloenzymes will be reviewed.     

Molecular molybdenum/bismuth compounds

Oxide-based materials containing molybdenum and bismuth exhibit unique chemical and physical properties; for instance, bismuthmolybdate phases represent efficient heterogeneous catalysts. This review therefore summarises the literature available concerning compounds containing Mo-Bi metal bonds on the one hand and complexes with bridging O-donor ligands (alkoxide or oxide) between Mo and Bi metal centres on the other hand. The structures adopted in the solid crystalline state are often determined by secondary interactions, which are discussed for certain series of compounds. Moreover, the reactivities observed are compared.     

Models for the molybdenum hydroxylases

 This commentary reviews structural, spectroscopic, and chemical models for the molybdenum hydroxylases. It briefly describes the current state of modeling and identifies areas where model chemistry may play a future role in understanding these enzymes. Received: 28 April 1997 / Accepted: 20 August 1997     

Involvement of organic molybdenum compounds in the interaction between copper, molybdenum, and sulfur

The effect on Cu metabolism of two organic Mo compounds, cysteine-Mo (CM) and cysteine-Mo-S (CMS), and of an inorganic compound, tetrathiomolybdate (TTM), was investigated in sheep. Intravenous administration of CMS or TTM increased total plasma Cu concentrations and promoted the appearance of trichloroacetic acid (TCA)-insoluble Cu in plasma. Plasma Mo was increased by both compounds. Column chromatography of plasma showed that CMS caused the accumulation of TCA-insoluble Cu in high-MW fractions, whereas TTM increased the Cu content of low-MW fractions, mainly albumin. CMS and TTM increased the concentration of Cu and Mo in kidney. In liver, Mo concentrations were elevated by both CMS and TTM, and Cu concentrations were reduced by TTM when it was given at a low dose rate. The subcellular distribution of Cu and Mo in liver and kidney was investigated. The findings are discussed in relation to the proposal that Mo-containing, organic compounds are intermediaries in the interaction between Cu, Mo, and S in ruminants.     

Determination of stable molybdenum isotopes by thermionic mass spectrometry for tracer studies of molybdenum plant metabolism

A tracer technique based on multiple stable Mo isotopes and thermionic quadrupole mass spectrometry for isotopic analysis of plant tissue was developed and has been applied in the long-term study of foliar absorption of Mo by potato plants. As several tracers have been used the multivariate linear regression methods has been applied to calculate the portions of tracer Mo present in the potato samples from the isotopic ratios measured and to estimate their reproducibilities.In this paper solely the tracer portions transferred from the leaf into the tuber of the potato have been determined. Dependent on the time of contamination, tracer portions of 0.2 to 12% have been measured, corresponding to a maximum of 2.3% of the foliar application of the tracer molybdate. The reproducibilities of the tracer method as a whole (analytical determination and calculation of the tracer portions in the tracer plant samples) amounted to 7% at the maximum (with one exception); by contrast, the individual differences between the three plants investigated were much larger (up to 80%).     

Molybdoenzymes and molybdenum cofactor in plants

The transition element molybdenum (Mo) is essential for (nearly) all organisms and occurs in more than 40 enzymes catalysing diverse redox reactions, however, only four of them have been found in plants. (1) Nitrate reductase catalyses the key step in inorganic nitrogen assimilation, (2) aldehyde oxidase(s) have been shown to catalyse the last step in the biosynthesis of the phytohormone abscisic acid, (3) xanthine dehydrogenase is involved in purine catabolism and stress reactions, and (4) sulphite oxidase is probably involved in detoxifying excess sulphite. Among Mo-enzymes, the alignment of amino acid sequences permits domains that are well conserved to be defined. With the exception of bacterial nitrogenase, Mo-enzymes share a similar pterin compound at their catalytic sites, the molybdenum cofactor. Mo itself seems to be biologically inactive unless it is complexed by the cofactor. This molybdenum cofactor combines with diverse apoproteins where it is responsible for the correct anchoring and positioning of the Mo-centre within the holo-enzyme so that the Mo-centre can interact with other components of the enzyme's electron transport chain. A model for the three-step biosynthesis of Moco involving the complex interaction of six proteins will be described. A putative Moco-storage protein distributing Moco to the apoproteins of Mo-enzymes will be discussed. After insertion, xanthine dehydrogenase and aldehyde oxidase, but not nitrate reductase and sulphite oxidase, require the addition of a terminal sulphur ligand to their Mo-site, which is catalysed by the sulphur transferase ABA3.