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2004 | 51 | 3 | 649-663
Article title

Kinetics and specificity of guinea pig liver aldehyde oxidase and bovine milk xanthine oxidase towards substituted benzaldehydes.

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EN
Abstracts
EN
Molybdenum-containing enzymes, aldehyde oxidase and xanthine oxidase, are important in the oxidation of N-heterocyclic xenobiotics. However, the role of these enzymes in the oxidation of drug-derived aldehydes has not been established. The present investigation describes the interaction of eleven structurally related benzaldehydes with guinea pig liver aldehyde oxidase and bovine milk xanthine oxidase, since they have similar substrate specificity to human molybdenum hydroxylases. The compounds under test included mono-hydroxy and mono-methoxy benzaldehydes as well as 3,4-dihydroxy-, 3-hydroxy-4-methoxy-, 4-hydroxy-3-methoxy-, and 3,4-dimethoxy-benzaldehydes. In addition, various amines and catechols were tested with the molybdenum hydroxylases as inhibitors of benzaldehyde oxidation. The kinetic constants have shown that hydroxy-, and methoxy-benzaldehydes are excellent substrates for aldehyde oxidase (Km values 5×10-6 M to 1×10-5 M) with lower affinities for xanthine oxidase (Km values around 10-4 M). Therefore, aldehyde oxidase activity may be a significant factor in the oxidation of the aromatic aldehydes generated from amines and alkyl benzenes during drug metabolism. Compounds with a 3-methoxy group showed relatively high Vmax values with aldehyde oxidase, whereas the presence of a 3-hydroxy group resulted in minimal Vmax values or no reaction. In addition, amines acted as weak inhibitors, whereas catechols had a more pronounced inhibitory effect on the aldehyde oxidase activity. It is therefore possible that aldehyde oxidase may be critical in the oxidation of the analogous phenylacetaldehydes derived from dopamine and noradrenaline.
Publisher

Year
Volume
51
Issue
3
Pages
649-663
Physical description
Dates
published
2004
received
2003-07-09
revised
2004-02-26
accepted
2004-03-25
Contributors
  • Department of Experimental Pharmacology, Medical School, Athens University, Athens, Greece
  • Department of Pharmaceutical Chemistry, School of Pharmacy, University of Bradford, Bradford, U.K.
References
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Document Type
Publication order reference
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YADDA identifier
bwmeta1.element.bwnjournal-article-abpv51i3p649kz
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