Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:1.17.3.2 (
xanthine oxidase
)
8,383
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
A quantitative structure-activity relationship for the reaction of
xanthine oxidase
with a homologous series of alpha, beta-unsaturated aldehydes, which are known to be products of lipid peroxidation, was investigated. Aldehydes in the series
2-butenal
through 2-nonenal and 4-hydroxy-2-nonenal, displayed differential reactivity toward
xanthine oxidase
as measured by production of the superoxide radical anion. Kinetic parameters for the rate of superoxide production and substrate affinity were determined via the superoxide dismutase-sensitive reduction of cytochrome c. Trends in kinetic parameters as a function of carbon number for the series of trans-2-enals was consistent with a dependence on substrate hydrophobicity. Log kw', a hydrophobicity constant widely employed as a model for the octanol/water partition coefficient, was determined by reversed phase liquid chromatography for the alpha, beta-unsaturated aldehydes in this study. Linear relationships for the correlation of substrate binding (pKm) and efficiency of superoxide production (log kcat/Km) with substrate hydrophobicity (log kw') were found. The mode of inhibition of xanthine oxidation by
2-butenal
is shown to be noncompetitive, suggesting distinct binding sites for purine and aldehydic substrates. It is suggested that the reaction of
xanthine oxidase
with unsaturated aldehydes could be an important route of amplification of oxidative damage in cells.
...
PMID:The reaction of xanthine oxidase with aldehydic products of lipid peroxidation. 166 61
