Molybdenum in enzymes

Studies bearing on the role of molybdenum in enzymes will be exemplified by a detailed summary of results on the most studied of these enzymes, which is undoubtedly milk xanthine oxidase. To put this in its context, it will be preceded by a review of the general properties of xanthine oxidase. The final section will then be a short account of work on some of the other molybdenum enzymes. 

Mechanistic speculations about the molybdoenzymes must be considered to be in their infancy with the possible exception of those for xanthine oxidase. Although the detailed structural nature of the molybdenum site is unknown, there is sufficient information from biochemical and coordination chemistry studies to allow informed arguments to be drawn. Here we first discuss evidence for the nuclearity of the molybdenum site and then discuss both oxo-transfer and proton-electron transfer mechanisms for molybdenum enzymes. A final discussion considers the unique aspects of nitrogenase and the possible reasons for the use of molybdenum in enzymes. 

Current concepts of the chemical nature and role of molybdenum-containing enzymes are reviewed. Methods for molybdenum in enzymes, spectroscopic manifestations of the metal, and the characteristics of molybdenum-deficient enzymes are discussed, with particular attention to xanthine oxidase, sulfite oxidase, and nitrate reductase, in which Mo5 (and Mo3 in some cases) species are readily demonstrated. Nitrogenase is presumed to use molybdenum in a catalytic step, but no direct evidence for its participation in catalysis is yet available. 

Stiefel, E. L, 1977a, Proposed molecular mechanism of die action of molybdenum in enzymes coupled proton and electron d ansfer, Proc. Nad. Acad. Sci. 70 988fi992. 

Coordination Compounds in Biology Table 23 Molybdenum in Enzymes... 

The function of molybdenum in enzymic mechanisms has been reviewed and the role of molybdenum in nitrogen fixation examined. ... 

Iron also occurs in conjunction with molybdenum in enzymes that catalyze nitrogen fixation. 

There is a growing interest in the involvement of metal ions and co-ordination compounds in biological systems, and this has been recognized in the United Kingdom by the inauguration of a new discussion group of the Dalton division of the Chemical Society. Some recent reviews are devoted to various aspects of this very broad field. Of relevance here are articles dealing with the kinetics and mechanism of metalloporphyrin formation, mechanisms for the reactions of molybdenum in enzymes, and a review of the chemistry of vitamin Bjg co-enzyme. A review has also appeared of the kinetics and mechanisms of substitution reactions in cobalt(ra)... 

Further work has been reported - with Fe-Mo models for nitro-genase, and a molecular mechanism has been proposed for the action of molybdenum in enzymes. In all reactions catalysed by Mo enzymes, the product and substrate differ by two electrons and two protons (or some multiple thereof). The co-ordination chemistry of Mo suggests that there is a distinct relationship between acid-base and redox properties of Mo complexes, and that a coupled electron-proton transfer (to or from substrate) may be mediated by Mo in enzymes. Each of the molybdenum enzymes (nitrogenase, nitrate reductase, xanthine oxidase, aldehyde oxidase, and sulphite oxidase) is discussed and it is shown that a simple molecular mechanism embodying coupled proton-electron transfer can explain many key experimental observations. 

In principle, combining EPR information with information from optical absorption spectroscopy ought to prove more definitive than does pure EPR. Unfortunately, absorption bands due to molybdenum in enzymes are weak and consequently have remained undetected beneath stronger absorb-tions from iron-sulfur, flavin, or heme centers. Therefore, the relatively recent finding that the heme-free molybdenum domain of the molecule may be isolated from sulfite oxidase by controlled proteolysis (Johnson and Rajag-opalan, 1977 see also Guiard and Lederer, 1977), is of very considerable interest One can only hope that it will prove possible, in due course, to collate the optical (Johnson and Rajagopalan, 1977) and EPR properties of such species. 

Table II summarizes all currently available data on the redox potentials of molybdenum in enzymes and other molybdenum-containing proteins. In all cases the values quoted were obtained by estimation, by EPR, of the fractional conversion of molybdenum to Mo(V) in a series of samples poised at known potentials. These potentials were measured with a platinum electrode, using a variety of low-molecular-weight dyes as mediators of the oxidation-reduction processes and usually with dithionite and ferricyanide...

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