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Differential catalytic properties in metabolism of endogenous and exogenous substrates among CYP3A enzymes expressed in COS-7 cells.
- Source :
-
Biochimica et biophysica acta [Biochim Biophys Acta] 1998 May 08; Vol. 1380 (3), pp. 297-304. - Publication Year :
- 1998
-
Abstract
- The catalytic properties of CYP3A7 in the metabolism of endogenous and exogenous substrates were compared with those of CYP3A4 and CYP3A5 using COS-7 expressing enzymes. The highest activities of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone 3-sulfate (DHEA-S) 16alpha-hydroxylase were observed in COS-7 cells expressing CYP3A7. In contrast, the activity of testosterone 6beta-hydroxylase of CYP3A7 expressed in COS-7 cells was much less than that of CYP3A4 expressed in COS-7 cells. The rate of carbamazepine 10, 11-epoxidation was the greatest in COS-7 cells expressing CYP3A4, followed by CYP3A5 and CYP3A7. On the other hand, the formation of reductive metabolite of zonisamide was the highest in COS-7 cells expressing CYP3A4, followed by CYP3A7 and CYP3A5. Furthermore, the addition of triazolam resulted in a decrease in 6beta-hydroxylation catalyzed by CYP3A7, but not by CYP3A4, whereas the pretreatment of microsomes with triacetyloleandomycin (TAO) resulted in a decrease in the reaction catalyzed by CYP3A4, but not by CYP3A7. Together with these results, it was suggested that CYP3A7 exerts differential catalytic properties not only in metabolism of endogenous substrates but also in drug metabolism compared to CYP3A4 and CYP3A5.<br /> (Copyright 1998 Elsevier Science B.V.)
- Subjects :
- Adult
Animals
COS Cells
Catalysis
Cytochrome P-450 CYP3A
Cytochrome P-450 Enzyme System analysis
Cytochrome P-450 Enzyme System genetics
DNA, Complementary genetics
Dehydroepiandrosterone metabolism
Enzyme Activation drug effects
Genetic Vectors metabolism
Humans
Mixed Function Oxygenases metabolism
Oxidoreductases, N-Demethylating genetics
Steroid 16-alpha-Hydroxylase
Steroid Hydroxylases metabolism
Substrate Specificity
Testosterone metabolism
Transfection
Triazolam pharmacology
Troleandomycin pharmacology
Aryl Hydrocarbon Hydroxylases
Cytochrome P-450 Enzyme System biosynthesis
Cytochrome P-450 Enzyme System metabolism
Oxidoreductases, N-Demethylating biosynthesis
Oxidoreductases, N-Demethylating metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0006-3002
- Volume :
- 1380
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Biochimica et biophysica acta
- Publication Type :
- Academic Journal
- Accession number :
- 9555064
- Full Text :
- https://doi.org/10.1016/s0304-4165(97)00156-6