[Theophylline metabolism by rat liver microsomal monooxygenases].
Theophylline metabolism has been studied in a reconstituted monooxygenase system with purified forms of cytochrome P-450: P-450a, P-450b, P-450d and P-450k as well as in liver microsomes of control and 3-methylcholanthrene-induced rats. Cytochrome P-450 isoforms, P-450a and P-450b, had no effect on theophylline metabolism, whereas forms P-450d and P-450k induced the synthesis of 1.3-dimethyluric acid (1.3-DMA) at the rates of 900 and 330 pmol/min/nmol of protein, respectively. The catalytic activity of these isoforms was fully inhibited by homologous monospecific antibodies. P-450c catalyzed the formation of a nonidentified metabolite. In microsomes of control animals antibodies specifically directed to cytochrome P-450k suppressed the rate of 1.3-DMA synthesis by 73%, whereas antibodies specifically raised against P-450c+d--by 11%. In microsomes of methylcholanthrene-induced animals the rate of 1.3-DMA synthesis was increased two-fold. This activity was inhibited by 61% by antibodies to cytochrome P-450k and by 18% by anti-P-450c+d antibodies.
Vavilin
V A
VA
Grishanova
A Iu
AIu
Guliaeva
L F
LF
Mishin
V M
VM
Liakhovich
D000818:Animals; D000911:Antibodies, Monoclonal; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000378:metabolism*; D004790:Enzyme Induction; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000096:biosynthesis / Q000378:metabolism*; D008297:Male; D008748:Methylcholanthrene; D008862:Microsomes, Liver / Q000201:enzymology*; D015260:Neprilysin / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013806:Theophylline / Q000378:metabolism*; D014527:Uric Acid / Q000031:analogs & derivatives / Q000378:metabolism
D000911:Antibodies, Monoclonal; D007527:Isoenzymes; D014527:Uric Acid; D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; D013806:Theophylline; C031274:1,3-dimethyluric acid; D015260:Neprilysin
Metabolizm teofillina mikrosomnymi monooksigenazami pecheni krys.