Metabolic functions molybdenum enzymes

An enzyme cofactor can be either an inorganic ion (usually a metal cation) or a small organic molecule called a coenzyme. In fact, the requirement of many enzymes for metal-ion cofactors is the main reason behind our dietary need for trace minerals. Iron, zinc, copper, manganese, molybdenum, cobalt, nickel, and selenium are all essential trace elements that function as enzyme cofactors. A large number of different organic molecules also serve as coenzymes. Often, although not always, the coenzyme is a vitamin. Thiamine (vitamin Bj), for example, is a coenzyme required in the metabolism of carbohydrates. 

Xanthine oxidase (EC 1.2.3.2) catalyzes the formation of uric acid, an end-product of purine catabolism. The mammalian enzyme is a metalloflavoprotein composed of two subunits containing molybdenum, FAD and Fe/S clusters as prosthetic groups in a ratio of 1 1 4 per subunit (1). Besides its endogenous metabolic function, xanthine oxidase is also active toward a wide spectrum of oxidizable xenobiotic substrates. Although some cestodes and trematodes produce trace amounts of uric acid (16), the presence of xanthine oxidase activity in these organisms has not been demonstrated. Xanthine oxidase was found in the cytosolic fractions of the nematodes Ancylostoma ceylanicum and Nippostrongylus brasiliensis (17), but its activity toward xenobiotic substrates was not tested. 

An inborn defect of metabolism that is closely related to sulfite oxidase deficiency and is more prevalent in the human population is that of molybdenum cofactor deficiency (Johnson 1997). In this disease syndrome, the activities of all molybdenum enzymes are affected owing to a lack of functional molybdopterin. The absence of sulfite oxidase is clearly most devastating. A number of individuals have been identified with xanthinuria (specific loss of XHD), and the resultant clinical symptoms are generally mild (Simmonds et al. 1995). A smaller class of patients has more recently been described with deficiencies in XHD and aldehyde oxidase, with mild clinical symptoms (Reiter et al. 1990). 

Although molybdenum and tungsten enzymes carry the name of a single substrate, they are often not as selective as this nomenclature suggests. Many of the enzymes process more than one substrate, both in vivo and in vitro. Several enzymes can function as both oxidases and reductases, for example, xanthine oxidases not only oxidize purines but can deoxygenate amine N-oxides [82]. There are also sets of enzymes that catalyze the same reaction but in opposite directions. These enzymes include aldehyde and formate oxidases/carboxylic acid reductase [31,75] and nitrate reductase/nitrite oxidase [83-87]. These complementary enzymes have considerable sequence homology, and the direction of the preferred catalytic reaction depends on the electrochemical reduction potentials of the redox partners that have evolved to couple the reactions to cellular redox systems and metabolic requirements. 

Calcium and phosphorus serve as structural components of bones and teeth and are thus required in relatively large quantities. Calcium (Ca ) plays many other roles in the body for example, it is involved in hormone action and blood clotting. Phosphorus is required for the formation of ATP and of phosphory-lated intermediates in metabolism. Magnesium activates many enzymes and also forms a complex with ATP. Iron is a particularly important mineral because it functions as a component of hemoglobin (the oxygen-carrying protein in the blood) and is part of many enzymes. Other minerals, such as zinc or molybdenum, are required in very small quantities (trace or ultra-trace amounts). 

The first indication of an essential metabolic role for molybdenum was obtained in 1953, when it was discovered that xanthine oxidase, important in purine metabolism, was a metalloenzyme containing molybdenum. Subsequently the element was shown to be a component of two other enzymes, aldehyde oxidase and sulphite oxidase. The biological functions of molybdenum, apart from its reactions with copper (see p. 123), are concerned with the formation and activities of these three enzymes. In addition to being a component of xanthine oxidase, molybdenum participates in the reaction of the enzyme with cytochrome C and also facilitates the reduction of cytochrome C by aldehyde oxidase. 

Molybdenum functions as the prosthetic group of a small number of enzymes, including xanthine oxidase (which is involved in the metabolism of purines to uric acid for excretion) and pyridoxal oxidase (which metabolizes vitamin to the inactive excretory product pyridoxic acid section 11.9.1). It occurs in an organic complex, molybdopterin, which is chemically similar to folic acid (section 11.11.1) but can be synthesized in the body as long as adequate amounts of molybdenum are available. 

EUNCTIONS OE MOLYBDENUM. Molybdenum is a component of three different enzyme systems which are involved in the metabolism of carbohydrates, fats, proteins, sulfur-containing amino acids, nucleic acids (DNA and RNA), and iron. Also, it is found in the enamel of teeth, where it appears to prevent or reduce the incidence of dental caries, although this function has not yet been proven conclusively. 

The essentiality of most of the elements mentioned above could have been confidently predicted from the discussions W e have developed in earlier chapters. Nitrogen and sulphur are constituent elements of proteins and many other cell constituents. The importance of phosphorus compounds such as nucleic acids, phospholipids and co-eri2ymes has been stressed several times. Magnesium is a constituent of the chlorophylls. Iron, copper, zinc, manganese and molybdenum are essential to the functioning of particular enzymes. In other cases, like that of calcium, their involvement in metabolism is less well understood and in still other cases, like potassium and boron, is almost completely obscure. 

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