[Individual and strain differences of aldehyde oxidase in the rat].
Together with xanthine oxidase, aldehyde oxidase (AO) is a major member of a relatively small family of molybdenum hydroxylases. Both enzymes are homodimers with a subunit molecular weight of about 150 kDa and exhibit catalytic activity only as a dimer. An AO subunit contains a molybdopterin cofactor, an FAD and two different 2Fe-2S redox centers. The enzyme catalyzes oxidation of a wide range of endogenous and exogenous aldehydes and N-heterocyclic aromatic compounds. N-heterocycle-containing drugs such as methotrexate, 6-mercaptopurine, cinchona alkaloids and famciclovir are oxidized by this enzyme. Marked species differences have been well documented for the AO-catalyzed metabolism of drugs including methotrexate and famciclovir. In addition, a large rat strain variation has also been demonstrated in the oxidation activity of benzaldehyde and methotrexate. Marked differences in species, large differences in rat strains and individual differences in AO activities in some rat strains have been reported. However, little has been elucidated about any related molecular biological mechanisms. We examined the mechanism of individual variations and strain difference of rat AO using the technology of molecular biology. Our recent studies regarding the inter- and intra-difference of AO activities in rats are described.
Itoh
Kunio
K
Department of Drug Metabolism and Pharmacokinetics, Tohoku Pharmaceutical University, Sendai, Japan. itoh-k@tohoku-pharm.ac.jp
D042931:Aldehyde Oxidase / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D003600:Cytosol / Q000201:enzymology; D018076:DNA, Complementary; D005787:Gene Frequency; D008099:Liver / Q000201:enzymology; D011110:Polymorphism, Genetic; D051381:Rats; D011919:Rats, Inbred Strains / Q000235:genetics*
D018076:DNA, Complementary; D042931:Aldehyde Oxidase