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Titolo:
INVOLVEMENT OF CYP3A1, 2B1, AND 2E1 IN C-8 HYDROXYLATION AND CYP 1A2 AND FLAVIN-CONTAINING MONOOXYGENASE IN N-DEMETHYLATION OF CAFFEINE - IDENTIFIED BY USING INDUCER TREATED RAT-LIVER MICROSOMES THAT ARE CHARACTERIZED WITH TESTOSTERONE METABOLIC PATTERNS
Autore:
CHUNG WG; ROH HK; KIM HM; CHA YN;
Indirizzi:
INHA UNIV,COLL MED,DEPT PHARMACOL & TOXICOL,NAM GU,253 YONGHYUN DONG INCHON 402751 SOUTH KOREA INHA UNIV,COLL MED,DEPT PHARMACOL & TOXICOL,NAM GU INCHON 402751 SOUTH KOREA INHA UNIV,COLL MED,MED TOXICOL RES CTR,NAM GU INCHON 402751 SOUTH KOREA INHA UNIV,COLL MED,DEPT INTERNAL MED,NAM GU INCHON 402751 SOUTH KOREA KOREA RES INST BIOSCI & BIOTECHNOL TAEJON SOUTH KOREA
Titolo Testata:
Chemico-biological interactions
fascicolo: 1, volume: 113, anno: 1998,
pagine: 1 - 14
SICI:
0009-2797(1998)113:1<1:IOC2A2>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
URINARY METABOLITES; CYTOCHROME-P-450; EXPRESSION; OXIDATION; INDUCTION; P450; CYTOCHROMES-P-450; BIOTRANSFORMATION; THEOPHYLLINE; ISOFORMS;
Keywords:
CAFFEINE OXIDATION; MICROSOMES; INDUCERS; CYTOCHROME P450; FLAVIN-CONTAINING MONOOXYGENASE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
28
Recensione:
Indirizzi per estratti:
Citazione:
W.G. Chung et al., "INVOLVEMENT OF CYP3A1, 2B1, AND 2E1 IN C-8 HYDROXYLATION AND CYP 1A2 AND FLAVIN-CONTAINING MONOOXYGENASE IN N-DEMETHYLATION OF CAFFEINE - IDENTIFIED BY USING INDUCER TREATED RAT-LIVER MICROSOMES THAT ARE CHARACTERIZED WITH TESTOSTERONE METABOLIC PATTERNS", Chemico-biological interactions, 113(1), 1998, pp. 1-14

Abstract

Caffeine (CA) is oxidized by rat liver microsomal enzymes to theobromine (TB), paraxanthine (PX), and theophylline (TP) by N-demethylation and to trimethylurate (TMU) by C-8 hydroxylation. In order to identifythe specific enzymes responsible for productions of these primary CA metabolites, liver microsomes enriched with various isoforms of cytochrome P450 (CYP) and flavin-containing monooxygenase (FMO) are preparedby pretreatment of rats with several inducers. The specific increasesin various CYP or FMO activities are identified with the diagnostic testosterone metabolic patterns or the thiobenzamide S-oxidation assay. They are then employed to metabolize the CA. Liver microsomes isolated from rats pretreated with phenobarbital (PB-microsomes) did not haveincreased FMO activity but had increased activities for hydroxylatingthe testosterone at 6 beta-(CYP3A1), 16 beta-(CYP2B1), and 2 beta-(CYP3A1) positions. This PB-microsomes had increased activity for TMU production from CA (result of C-8 hydroxylation). Liver microsomes isolated from rats pretreated with acetone (AC-microsomes) had a normal level of FMO activity but had enhanced rates of 6 beta-(CYP3A1) and 2 beta-(CYP3A1) hydroxylations of testosterone. The AC-microsomes again had increased activity for production of TMU. Similarly, the liver microsomes isolated from rats pretreated with dexamethasone (DEX-microsomes) had a normal level of FMO activity but had enhanced rates of forming 6beta- and 2 beta-hydroxytestosterone (CYP3A1) as well as androstenedione (CYP3A1). The DEX-microsomes again had increased activity for production of TMU only. Liver microsomes isolated from rats pretreated with 3-methylcholanthrene (MC-microsomes), however had increased FMO activity and also enhanced rates of forming the 7 alpha-(CYP1A1/2, and 2A1), 6 beta-(CYP3A1), and 2 beta-(CYP3A1) hydroxytestosterone. The MC-microsomes had increased activity for producing all of the four primary metabolites of CA, i.e. the N-demethylation metabolites like TB, PX, and TP, as well as the C-8 hydroxylation metabolite TMU. By the processof association of the obtained results, liver microsomes with increased contents of CYP2B1, 3A1, and 2E1 could catalyze the C-S hydroxylation at an increased rate producing increased amount of TMU. Increased productions of CA N-demethylation metabolites (TB, PX, and TP) are, however, catalyzed by the increased activities of CYP1A2 and FMO which are associated uniquely with the MC-microsomes. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 26/01/20 alle ore 01:03:41