Localization of xanthine oxidase in mammary-gland epithelium and capillary endothelium

Jarasch, Ernst-Dieter; Gründ, Christine; Bruder, Gerda; Heid, Hans; Keenan, T.W.; Franke, Werner W.

doi:10.1016/0092-8674(81)90232-4

Cited by 404 publications

(184 citation statements)

References 42 publications

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“…Moco is required for the activity of sulfite oxidase, xanthine dehydrogenase, and aldehyde oxidase in humans. Although xanthine dehydrogenase was shown to be a cytosolic protein (22), sulfite oxidase, one of the major target proteins for Moco, was shown to be localized in the intermembrane space of mitochondria (23). It remains speculative whether the insertion of Moco into sulfite oxidase occurs in the cytosol or in the mitochondrial intermembrane space.…”

Section: Discussionmentioning

confidence: 99%

Evidence for the physiological role of a rhodanese-like protein for the biosynthesis of the molybdenum cofactor in humans

Matthies

Rajagopalan

Mendel

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

126

149

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Recent studies have identified the human genes involved in the biosynthesis of the molybdenum cofactor. The human MOCS3 protein contains an N-terminal domain similar to the Escherichia coli MoeB protein and a C-terminal segment displaying similarities to the sulfurtransferase rhodanese. The MOCS3 protein is believed to catalyze both the adenylation and the subsequent generation of a thiocarboxylate group at the C terminus of the smaller subunit of molybdopterin (MPT) synthase. The MOCS3 rhodanese-like domain (MOCS3-RLD) was purified after heterologous expression in E. coli and was shown to catalyze the transfer of sulfur from thiosulfate to cyanide. In a defined in vitro system for the generation of MPT from precursor Z, the sulfurated form of MOCS3-RLD was able to provide the sulfur for the thiocarboxylation of MOCS2A, the small MPT synthase subunit in humans. Mutation of the putative persulfide-forming active-site cysteine residue C412 abolished the sulfurtransferase activity of MOCS3-RLD completely, showing the importance of this cysteine residue for catalysis. In contrast to other mammalian rhodaneses, which are mostly localized within mitochondria, MOCS3 in addition to the subunits of MPT synthase are localized in the cytosol.

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Section: Discussionmentioning

confidence: 99%

Evidence for the physiological role of a rhodanese-like protein for the biosynthesis of the molybdenum cofactor in humans

Matthies

Rajagopalan

Mendel

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

126

149

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“…Until relatively recently, XOR has been generally assumed to be exclusively cytoplasmic (44), where XDH predominates (34). In this context, XDH would certainly be more efficient than XO as a catalyst of NO production, at least with NADH as reducing substrate (Table I).…”

Section: Discussionmentioning

confidence: 99%

Reduction of Nitrite to Nitric Oxide Catalyzed by Xanthine Oxidoreductase

Godber¹,

Doel²,

Sapkota³

et al. 2000

Journal of Biological Chemistry

376

288

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Xanthine oxidase (XO) was shown to catalyze the reduction of nitrite to nitric oxide (NO), under anaerobic conditions, in the presence of either NADH or xanthine as reducing substrate. NO production was directly demonstrated by ozone chemiluminescence and showed stoichiometry of approximately 2:1 versus NADH depletion. With xanthine as reducing substrate, the kinetics of NO production were complicated by enzyme inactivation, resulting from NO-induced conversion of XO to its relatively inactive desulfo-form. Steady-state kinetic parameters were determined spectrophotometrically for urate production and NADH oxidation catalyzed by XO and xanthine dehydrogenase in the presence of nitrite under anaerobic conditions. pH optima for anaerobic NO production catalyzed by XO in the presence of nitrite were 7.0 for NADH and <6.0 for xanthine. Involvement of the molybdenum site of XO in nitrite reduction was shown by the fact that alloxanthine inhibits xanthine oxidation competitively with nitrite. Strong preference for Mo‫؍‬S over Mo‫؍‬O was shown by the relatively very low NADH-nitrite reductase activity shown by desulfo-enzyme. The FAD site of XO was shown not to influence nitrite reduction in the presence of xanthine, although it was clearly involved when NADH was the reducing substrate. Apparent production of NO decreased with increasing oxygen tensions, consistent with reaction of NO with XO-generated superoxide. It is proposed that XO-derived NO fulfills a bactericidal role in the digestive tract.

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“…There are, however, major differences between the two "reperfusion injury" theories in defining the mechanistic role of xanthine oxidase. First, the site ofXOD activity is shifted from the hepatocyte to the endothelial cell; in this context, it should be noted that the hepatic localization of XOD is still a topic of controversy (43)(44)(45)(46). Second, the putative role of XOD would now be in signal transduction rather than in direct free radical-mediated injury.…”

Section: Discussionmentioning

confidence: 99%

Enhanced activity of the free radical producing enzyme xanthine oxidase in hypoxic rat liver. Regulation and pathophysiologic significance.

Brass

Narciso²,

Gollan³

1991

J. Clin. Invest.

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It has been widely proposed that conversion of xanthine dehydrogenase (XDH) to its free radical-producing form, xanthine oxidase (XOD), underlies ischemic/reperfusion injury, although the relationship of this conversion to hypoxia and its physiologic control have not been defined. This study details the time course and control of this enzymatic interconversion. In a functionally intact, isolated perfused rat liver model, mean % XOD activity increased as a function of both the duration (25 to 45% in 3 h) and degree (r = 0.97) of hypoxia. This process was markedly accelerated in ischemic liver by an overnight fast (45 vs. 30% at 2 h), and by imposing a short period of in vivo ischemia (cardiopulmonary arrest 72%). Moreover, only under these conditions was there a significant rise in the XOD activity due to the conformationally altered XDH molecule (XODc, 18%), as well as concomitant morphologic injury. Neither circulating white blood cells nor thrombosis appeared to contribute to the effects of in vivo ischemia on enzyme conversion. Thus, it is apparent that conversion to the free radical-producing state, with high levels of XOD activity and concurrent cellular injury, can be achieved during a relatively short period of hypoxia under certain well-defined physiologic conditions, in a time course consistent with its purported role in modulating reperfusion injury. These data also suggest that the premorbid condition of organ donors (e.g., nutritional status and relative state of hypoxia) is important in achieving optimal organ preservation. (J. Clin. Invest. 1991. 87:424-431.)

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Localization of xanthine oxidase in mammary-gland epithelium and capillary endothelium

Cited by 404 publications

References 42 publications

Evidence for the physiological role of a rhodanese-like protein for the biosynthesis of the molybdenum cofactor in humans

Evidence for the physiological role of a rhodanese-like protein for the biosynthesis of the molybdenum cofactor in humans

Reduction of Nitrite to Nitric Oxide Catalyzed by Xanthine Oxidoreductase

Enhanced activity of the free radical producing enzyme xanthine oxidase in hypoxic rat liver. Regulation and pathophysiologic significance.

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