Characterization of pig liver purified cytochrome P-450 isoenzymes for ochratoxin A metabolism studies.
In this paper, we report the characterization of 4 isolated, constitutive cytochrome P-450 fractions from pig liver microsomes. The two predominant forms, A2 and A3, exhibit several similarities: a Mr of 54 kDa, a lambda max CO-Fe++ at 448 nm, a relatively high ratio of the high-spin form and an immunological cross-reaction with polyclonal antibodies against rat liver P-450 IIB1. It is shown that these forms and the minor form Ba, which are active as benzphetamine N-demethylase, play an important metabolic role in ochratoxin A oxidation. This mycotoxin was oxidized by at least 3 different pig liver cytochrome P-450 fractions, each producing different metabolites, namely (4R)-, (4S)-hydroxyochratoxin A, and a new lipophilic metabolite. Since the pig is particularly susceptible to ochratoxin A toxicity, it represents a good animal model for in vitro studies of the metabolism of such a xenobiotic.
Oster
T
T
Centre du Médicament, URA CNRS 597, Faculté des Sciences Pharmaceutiques et Biologiques, Université de Nancy I, France.
Jayyosi
Z
Z
Creppy
E E
EE
el Amri
H S
HS
Batt
A M
AM
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000302:isolation & purification* / Q000378:metabolism; D007527:Isoenzymes / Q000302:isolation & purification* / Q000378:metabolism; D008862:Microsomes, Liver / Q000201:enzymology* / Q000378:metabolism; D009793:Ochratoxins / Q000378:metabolism*; D013552:Swine
D007527:Isoenzymes; D009793:Ochratoxins; C025589:ochratoxin A; D003577:Cytochrome P-450 Enzyme System