Cargando…
Chemical Nature and Reaction Mechanisms of the Molybdenum Cofactor of Xanthine Oxidoreductase
Xanthine oxidoreductase (XOR), a complex flavoprotein, catalyzes the metabolic reactions leading from hypoxanthine to xanthine and from xanthine to urate, and both reactions take place at the molybdenum cofactor. The enzyme is a target of drugs for therapy of gout or hyperuricemia. We review the che...
Autores principales: | , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Bentham Science Publishers
2013
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3624778/ https://www.ncbi.nlm.nih.gov/pubmed/23116398 http://dx.doi.org/10.2174/1381612811319140010 |
_version_ | 1782266054090686464 |
---|---|
author | Okamoto, Ken Kusano, Teruo Nishino, Takeshi |
author_facet | Okamoto, Ken Kusano, Teruo Nishino, Takeshi |
author_sort | Okamoto, Ken |
collection | PubMed |
description | Xanthine oxidoreductase (XOR), a complex flavoprotein, catalyzes the metabolic reactions leading from hypoxanthine to xanthine and from xanthine to urate, and both reactions take place at the molybdenum cofactor. The enzyme is a target of drugs for therapy of gout or hyperuricemia. We review the chemical nature and reaction mechanisms of the molybdenum cofactor of XOR, focusing on molybdenum-dependent reactions of actual or potential medical importance, including nitric oxide (NO) synthesis. It is now generally accepted that XOR transfers the water-exchangeable -OH ligand of the molybdenum atom to the substrate. The hydroxyl group at OH-Mo(IV) can be replaced by urate, oxipurinol and FYX-051 derivatives and the structures of these complexes have been determined by x-ray crystallography under anaerobic conditions. Although formation of NO from nitrite or formation of xanthine from urate by XOR is chemically feasible, it is not yet clear whether these reactions have any physiological significance since the reactions are catalyzed at a slow rate even under anaerobic conditions. |
format | Online Article Text |
id | pubmed-3624778 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Bentham Science Publishers |
record_format | MEDLINE/PubMed |
spelling | pubmed-36247782013-04-15 Chemical Nature and Reaction Mechanisms of the Molybdenum Cofactor of Xanthine Oxidoreductase Okamoto, Ken Kusano, Teruo Nishino, Takeshi Curr Pharm Des Article Xanthine oxidoreductase (XOR), a complex flavoprotein, catalyzes the metabolic reactions leading from hypoxanthine to xanthine and from xanthine to urate, and both reactions take place at the molybdenum cofactor. The enzyme is a target of drugs for therapy of gout or hyperuricemia. We review the chemical nature and reaction mechanisms of the molybdenum cofactor of XOR, focusing on molybdenum-dependent reactions of actual or potential medical importance, including nitric oxide (NO) synthesis. It is now generally accepted that XOR transfers the water-exchangeable -OH ligand of the molybdenum atom to the substrate. The hydroxyl group at OH-Mo(IV) can be replaced by urate, oxipurinol and FYX-051 derivatives and the structures of these complexes have been determined by x-ray crystallography under anaerobic conditions. Although formation of NO from nitrite or formation of xanthine from urate by XOR is chemically feasible, it is not yet clear whether these reactions have any physiological significance since the reactions are catalyzed at a slow rate even under anaerobic conditions. Bentham Science Publishers 2013-04 2013-04 /pmc/articles/PMC3624778/ /pubmed/23116398 http://dx.doi.org/10.2174/1381612811319140010 Text en © 2013 Bentham Science Publishers http://creativecommons.org/licenses/by/2.5/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.5/), which permits unrestrictive use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Article Okamoto, Ken Kusano, Teruo Nishino, Takeshi Chemical Nature and Reaction Mechanisms of the Molybdenum Cofactor of Xanthine Oxidoreductase |
title | Chemical Nature and Reaction Mechanisms of the Molybdenum Cofactor of Xanthine Oxidoreductase |
title_full | Chemical Nature and Reaction Mechanisms of the Molybdenum Cofactor of Xanthine Oxidoreductase |
title_fullStr | Chemical Nature and Reaction Mechanisms of the Molybdenum Cofactor of Xanthine Oxidoreductase |
title_full_unstemmed | Chemical Nature and Reaction Mechanisms of the Molybdenum Cofactor of Xanthine Oxidoreductase |
title_short | Chemical Nature and Reaction Mechanisms of the Molybdenum Cofactor of Xanthine Oxidoreductase |
title_sort | chemical nature and reaction mechanisms of the molybdenum cofactor of xanthine oxidoreductase |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3624778/ https://www.ncbi.nlm.nih.gov/pubmed/23116398 http://dx.doi.org/10.2174/1381612811319140010 |
work_keys_str_mv | AT okamotoken chemicalnatureandreactionmechanismsofthemolybdenumcofactorofxanthineoxidoreductase AT kusanoteruo chemicalnatureandreactionmechanismsofthemolybdenumcofactorofxanthineoxidoreductase AT nishinotakeshi chemicalnatureandreactionmechanismsofthemolybdenumcofactorofxanthineoxidoreductase |