Molecular characterization of human xanthine oxidoreductase: the enzyme is grossly deficient in molybdenum and substantially deficient in iron-sulphur centres

Godber, Benjamin L. J.; Schwarz, Günter; Mendel, Ralf R.; Lowe, David J.; Bray, Robert C.; Eisenthal, Robert; Harrison, Roger

doi:10.1042/bj20041984

Cited by 31 publications

(34 citation statements)

References 48 publications

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“…Both enzymes belong to a molybdenum hydroxylase family as mentioned above, are structurally similar, and have identical X-ray absorption spectra indicative of the same ligand environment and coordination geometry around molybdenum center. The crystal structures of XOR in the two forms, dehydrogenase and oxidase, have been solved after successful crystallization of both forms of the enzyme, to clarify the structure-based mechanism of conversion Enroth et al, 2000;Truglio et al, 2002;Kuwabara et al, 2003;Okamoto et al, 2004;Godber et al, 2005) (Fig. 2).…”

Section: Introduction Historical Backgroundmentioning

confidence: 99%

Therapeutic Effects of Xanthine Oxidase Inhibitors: Renaissance Half a Century after the Discovery of Allopurinol

2006

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Section: Introduction Historical Backgroundmentioning

confidence: 99%

Therapeutic Effects of Xanthine Oxidase Inhibitors: Renaissance Half a Century after the Discovery of Allopurinol

2006

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“…Alternatively, it may reflect the real presence of a large pool of inactive enzyme in chicken kidney. This is not unprecedented, as high levels of catalytically inactive XOR have been reported in milk (10,44). In this biological fluid, inactive XOR results presumably from the loss of the terminal MoCo sulfur ligand, which is likely to be present in chicken AOX1, as well as many other mammalian aldehyde oxidases.…”

Section: Purification Of Chicken Kidney Aox1 Demonstrates That the Prmentioning

confidence: 86%

Avian and Canine Aldehyde Oxidases

Terao¹,

Kurosaki²,

Barzago

et al. 2006

Journal of Biological Chemistry

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Aldehyde oxidases are molybdo-flavoenzymes structurally related to xanthine oxidoreductase. They catalyze the oxidation of aldehydes or N-heterocycles of physiological, pharmacological, and toxicological relevance. Rodents are characterized by four aldehyde oxidases as follows: AOX1 and aldehyde oxidase homologs 1-3 (AOH1, AOH2, and AOH3). Humans synthesize a single functional aldehyde oxidase, AOX1. Here we define the structure and the characteristics of the aldehyde oxidase genes and proteins in chicken and dog. The avian genome contains two aldehyde oxidase genes, AOX1 and AOH, mapping to chromosome 7. AOX1 and AOH are structurally very similar and code for proteins whose sequence was deduced from the corresponding cDNAs. AOX1 is the ortholog of the same gene in mammals, whereas AOH represents the likely ancestor of rodent AOH1, AOH2, and AOH3. The dog genome is endowed with two structurally conserved and active aldehyde oxidases clustering on chromosome 37. Cloning of the corresponding cDNAs and tissue distribution studies demonstrate that they are the orthologs of rodent AOH2 and AOH3. The vestiges of dog AOX1 and AOH1 are recognizable upstream of AOH2 and AOH3 on the same chromosome. Comparison of the complement and the structure of the aldehyde oxidase and xanthine oxidoreductase genes in vertebrates and other animal species indicates that they evolved through a series of duplication and inactivation events. Purification of the chicken AOX1 protein to homogeneity from kidney demonstrates that the enzyme possesses retinaldehyde oxidase activity. Unlike humans and most other mammals, dog and chicken are devoid of liver aldehyde oxidase activity. Molybdo-flavoenzymes (MOFEs)4 constitute a small family of homodimeric oxidoreductases characterized by conserved structures (1). Until a few years ago, it was believed that the family of mammalian MOFEs consisted of only two members, i.e. xanthine oxidoreductase (XOR) (2-4) and the aldehyde oxidase AOX1 5 (5-8). XOR has been extensively studied and is the key enzyme in the catabolism of purines, oxidizing hypoxanthine to xanthine and xanthine to uric acid (9 -14). This function is conserved throughout evolution, as the enzyme is present from bacteria to man (1). In mammals, the protein also plays an important role in milk secretion (15-17) and kidney development (18). The function of AOX1 is ill-defined, and the enzyme lacks a recognized physiological substrate. AOX1 metabolizes N-heterocyclic compounds and aldehydes of pharmacological and toxicological relevance (19 -22). XOR and AOX1 are the products of two genes mapping on distinct chromosomes in rodents and different arms of chromosome 2 in humans (4,7,23,24).Recently, we demonstrated that the family of mammalian MOFEs is larger than originally anticipated (25-28). Mice and rats are endowed with three extra MOFEs structurally and biochemically more similar to AOX1 than to XOR. We named these proteins aldehyde oxidase homologs 1-3 (AOH1, AOH2, and AOH3). In rodents, AOH1 is synthesized predominantly in liver and...

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“…The XOR level in milk differs recognizably during lactation. However, bovine milk contains significant levels of XOR (1.4-1.8 U/mg) as compared to goat (0.27 U/mg) and sheep (0.69 U/mg) milk and camel (nd) milk because enzyme molecules lack molybdenum (Mo ++ ) [115][116][117][118]. This level can be amplified by complementing the diet with Mo ++ [7].…”

Section: Xanthine Oxidoreductasementioning

confidence: 99%

Lactation Responses toward Milk Indigenous Enzymes

Hameed¹,

Hussain²,

Akhtar³

2017

Livestock Science

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Milk being a highly nutritious food in its natural form provides energy. There are various factors influencing the composition of milk: breed, stage of lactation, nutritional status, health, and milking intervals. A number of indigenous enzymes present in milk are being affected by stages of lactation period. Their concentration varies during early, mid and late lactation periods. This varied behavior ultimately affects the quality of dairy products. In this chapter, the level of milk enzymes: lipases and esterases, plasmin (PL), plasminogen (PLG) phosphatases (alkaline phosphatase ALP; acid phosphatase (ACP), lysozyme (LZ), lactoperoxidase (LP), xanthine oxidoreductase (XOR), and catalase (CAT) will be reviewed with respect to the stages of lactation periods.

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Molecular characterization of human xanthine oxidoreductase: the enzyme is grossly deficient in molybdenum and substantially deficient in iron-sulphur centres

Cited by 31 publications

References 48 publications

Therapeutic Effects of Xanthine Oxidase Inhibitors: Renaissance Half a Century after the Discovery of Allopurinol

Therapeutic Effects of Xanthine Oxidase Inhibitors: Renaissance Half a Century after the Discovery of Allopurinol

Avian and Canine Aldehyde Oxidases

Lactation Responses toward Milk Indigenous Enzymes

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