Aldehyde oxidase molybdenum

Molybdenum is required in the diet. It is required by three enzymes in mammals sulfite oxidase, xanthine dehydrogenase, and aldehyde oxidase. Molybdenum occurs in these enzymes as part of the molybdenum cofactor (Figure 10.52). This cofactOT is biosynthes z.ed in the body with GTP as the starling material. All known Mo mclalloenzymes, with the exception of nitrogenase (a plant enzyme), use Mo in the form of the molybdenum cofactor. 

Molybdenum. Molybdenum is a component of the metaHoen2ymes xanthine oxidase, aldehyde oxidase, and sulfite oxidase in mammals (130). Two other molybdenum metaHoen2ymes present in nitrifying bacteria have been characteri2ed nitrogenase and nitrate reductase (131). The molybdenum in the oxidases, is involved in redox reactions. The heme iron in sulfite oxidase also is involved in electron transfer (132). 

Of the mammalian enzymes, the sulphite oxidase of bovine liver has only recently been discovered to contain molybdenum (15). The better known molybdenum enzymes, xanthine oxidase from cows milk (31) and aldehyde oxidase from rabbit liver (16) are closely related to one another as they are to the xanthine dehydrogenases from chicken liver (17) and from bacteria (18). 

So little is known about molybdenum enzymes other than milk xanthine oxidase that there is little to be said by way of general conclusions. In all cases where there is direct evidence (except possibly for xanthine dehydrogenase from Micrococcus lactilyticus) it seems that molybdenum in the enzymes does have a redox function in catalysis. For the xanthine oxidases and dehydrogenases and for aldehyde oxidase, the metal is concerned in interaction of the enzymes with reducing substrates. However, for nitrate reductase it is apparently in interaction with the oxidizing substrate that the metal is involved. In nitrogenase the role of molybdenum is still quite uncertain. 

Molybdenum Milk, milk products dried legumes or pulses liver and kidney grains Prosthetic group of enzymes aldehyde oxidase Xanthine oxidase Electron transfer chain enzymes... 

METHOD OF CONTINUOUS VARIATION MOLYBDENUM COFACTOR (MoCo) Molybdenum-dependent reactions, ALDEHYDE OXIDASE MOLYBDOPTERIN NITRATE REDUCTASE NITROGENASE SULFITE OXIDASE XANTHINE DEHYDROGENASE MOLYBDOPTERIN... 

The monooxygenase group of enzymes includes the non-P450 hydroxylases which catalyze the insertion of a hydroxyl group to replace a hydrogen atom at a saturated carbon [6-8] and the non-heme-dependent oxygenases such as the flavin-molybdenum-cobalt-dependent xanthine oxidase and aldehyde oxidase... 

In addition to these classical aromatic ring hydroxylations, many nitrogen heterocycles are substrates for molybdenum-containing enzymes, such as xanthine oxidase and aldehyde oxidase, which are present in the hepatic cytosolic fractions from various animal species. The molybdenum hydroxylases (B-75MI10902) catalyze the oxidation of electron-deficient carbons in aromatic nitrogen heterocycles. The reactions catalyzed by these enzymes are generally represented by equations (2) and (3). 

Coughlan, M. P. 1980. Aldehyde oxidase, xanthine oxidase and xanthine dehydrogenase. Hydroxylases containing molybdenum, iron-sulphur and flavin. In Molybdenum and Molybdenum-Containing Enzymes. M.P. Coughlan (Editor). Pergamon Press, Oxford, pp. 119-185. 

Fe prosthetic groups.282 283 A group of aldehyde oxidases and xanthine dehydrogenases also contain molybdenum as well as iron (Chapter 16). In every case the metal ions are bound independently of the flavin.2833... 

Long recognized as an essential element for the growth of plants, molybdenum has never been directly demonstrated as a necessary animal nutrient. Nevertheless, it is found in several enzymes of the human body, as well as in 30 or more additional enzymes of bacteria and plants.632 Aldehyde oxidases,633 xanthine oxidase of liver and the related xanthine dehydrogenase, catalyze the reactions of Eqs. 16-58 and 16-59 and contain molybdenum that is essential for catalytic activity. Xanthine oxidase also contains two Fe2S2 clusters and bound FAD. The enzymes can also... 

Other enzymes in the soluble fraction of liver that oxidize aldehydes are aldehyde oxidase and xanthine oxidase, both flavoproteins that contain molybdenum however, their primary role seems to be the oxidation of endogenous aldehydes formed as a result of deamination reactions. 

Molybdenum is a component of at least three enzymes aldehyde oxidase, xanthine dehydrogenase, and sulfite oxidase. The first two contain FAD, whereas the last is a heme protein similar to cytochrome c. Xanthine dehydrogenase can also act as an oxidase, that is, it can use 02 as an electron acceptor. Physiologically, however, it uses NAD+ as an electron acceptor when it converts hypoxanthine to xanthine and the latter to uric acid (see Chapter 10). Aldehyde and sulfite oxidases are true oxidases physiologically they both use 02 as an electron acceptor. Molybdenum in all three enzymes is associated with a pterinlike cofactor whose structure is shown in Figure 6.11. The Mo cofactor cannot be... 

Figure 6.11 Structure of the pterin cofactor, which binds molybdenum in aldehyde oxidase, xanthine oxidase, and sulfite oxidase. [Reproduced by permission from Rajago-palan, KV. Molybdenum, an essential trace element. Nutr. Rev., 45 321-328 (1987).]...

Evidence Concerning the Molybdenum Site. Despite considerable debate, there is at present a good deal of agreement as to the overall mode of functioning of xanthine oxidase (20, 65-70). Furthermore, the EPR spectroscopic properties indicate that the molybdenum sites in aldehyde oxidase and (to a somewhat lesser extent) sulfite oxidase are very similar in nature to that in xanthine oxidase. 

The other molybdenum enzymes each contain duplicate prosthetic groups and paired subunits in addition to two molybdenum atoms. Many of the experiments performed for xanthine oxidase have also been carried out with aldehyde oxidase and sulfite oxidase, and there is no evidence for chemical Mo-Mo coupling in these enzymes. Thus, in oxidases, the evidence for mononuclear molybdenum sites appears strong, and in view of the duplicate subunits and composition found, it is reasonable to assume a similar situation in reductases as well. However, at present, insufficient information bars a full generalization. 

Several decades ago, the earliest genetic work in molybdenum enzymes identified mutants of two fungi, Aspergillus nidulans (125) and Neurospora crassa (126) that lacked all molybdenum enzyme activities, specifically, nitrate reductase, XDH, and aldehyde oxidase. The mutant N. crassa produces an... 

Molybdenum plays a role in several enzyme reactions. Some of the molybdenum-containing enzymes are aldehyde oxidase, sulfite oxidase, xanthine dehydrogenase, and xanthine oxidase. This metal is found in cereal grains and legumes leafy vegetables, especially those rich in chlorophyll animal organs and in relatively small amounts, less than 0.1 ppm, in fruits. The molybdenum content of foods is subject to large variations. 

Molybdenum Hydroxylases (Aldehyde Oxidase, Xanthine Oxidase) Oxidations Purines, pteridine, methrotrexate, quinolones, 6-deoxycyclovir... 

In addition to liver aldehyde dehydrogenase, a number of other enzymes present in the soluble fraction of liver homogenates will oxidize aldehydes and certain N-heterocyclic compounds. Among these are aldehyde oxidase and xanthine oxidase (see below), both flavoprotein enzymes containing molybdenum. These enzymes catalyze the oxidation of aldehydes formed by the deamination of endogenous amines by amine oxidases. 

There are a number of molybdenum-containing enzymes, but those that are important in carbon oxidation of xenobiotics are aldehyde oxidase (AO) and xanthine oxidase (XO), also referred to as molybdenum hydroxylases (Figure 10.7). Both enzymes catalyze the oxidation of a wide range of aldehydes and N-heterocycles. The name aldehyde oxidase is somewhat misleading, however, because oxidation of heteroaromatics is more significant. The differences in substrate specificities between... 

Aldehyde oxidase purified from maize coleoptiles is a multicomponent enzyme that contains a molybdenum cofactor, nonheme iron, and flavin adenine dinucleotide (FAD) as prosthetic groups.111 When substrate specificity of the aldehyde oxidase was tested, good activity was detected with IAAld, indole-3-aldehyde, and benzaldehyde among others. The addition of NADP and NADPH did not change the activity. In contrast, in maize endosperm, tryptophan-dependent IAA biosynthesis was dependent on an NADP/NADPH redox system, which may mean that the two tissues of maize are utilizing different pathways or different redox systems for IAA biosynthesis.112... 

Three human redox enzymes, and a variety of bacterial enzymes, contain molybdenum chelated by two sulfur atoms in a modified pterin molybdopterin (see Figure 10.1). In sulfite oxidase, the other two chelation sites of the molybdenum are occupied by oxygen in xanthine oxidase / dehydrogenase (Section 7.3.7) and aldehyde oxidase, one site is occupied by oxygen and one by sulfur. In some bacterial enzymes, molybdopterin occurs as a guanine dinucleotide rather than free. In others, tungsten rather than molybdopterin is the chelated metal there is no evidence that any mammalian enzymes contain tungsten. 

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