Mechanistic insights into xanthine oxidoreductase from development studies of candidate drugs to treat hyperuricemia and gout.

Abstract

Xanthine oxidoreductase (XOR), which is widely distributed from humans to bacteria, has a key role in purine catabolism, catalyzing two steps of sequential hydroxylation from hypoxanthine to xanthine and from xanthine to urate at its molybdenum cofactor (Moco). Human XOR is considered to be a target of drugs not only for therapy of hyperuricemia and gout, but also potentially for a wide variety of other diseases. In this review, we focus on studies of XOR inhibitors and their implications for understanding the chemical nature and reaction mechanism of the Moco active site of XOR. We also discuss further experimental or clinical studies that would be helpful to clarify remaining issues.

• Authors: Takeshi Nishino, Ken Okamoto
• Journal: Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry (J Biol Inorg Chem) Vol. 20 Issue 2 Pg. 195-207 (Mar 2015) ISSN: 1432-1327 [Electronic] Germany
• PMID: 25501928 (Publication Type: Journal Article, Review)

Chemical References

• Coenzymes
• Enzyme Inhibitors
• Metalloproteins
• Molybdenum Cofactors
• Pteridines
• Xanthine
• molybdenum cofactor
• Xanthine Dehydrogenase

Topics

• Catalytic Domain
• Coenzymes (chemistry, metabolism)
• Enzyme Inhibitors (therapeutic use)
• Gout (drug therapy, enzymology, pathology)
• Humans
• Hyperuricemia (drug therapy, enzymology, pathology)
• Metalloproteins (chemistry, metabolism)
• Molybdenum Cofactors
• Pteridines (chemistry, metabolism)
• Xanthine (chemistry)
• Xanthine Dehydrogenase (antagonists & inhibitors, chemistry, metabolism)