scholarly journals Effects of Cytochrome P450 Inhibitors on the Biotransformation of Fluorogenic Substrates by Adult Male Rat Liver Microsomes and cDNA-Expressed Rat Cytochrome P450 Isoforms

2009 ◽  
Vol 113 (2) ◽  
pp. 293-304 ◽  
Author(s):  
Emilija Makaji ◽  
Cristina S. Trambitas ◽  
Pamela Shen ◽  
Alison C. Holloway ◽  
Denis J. Crankshaw
Keyword(s):  
Cytochrome P450 ◽  
Rat Liver ◽  
Adult Male ◽  
Liver Microsomes ◽  
Male Rat ◽  
Rat Liver Microsomes ◽  
Fluorogenic Substrates ◽  
Cytochrome P450 Isoforms ◽  
Adult Male Rat ◽  
P450 Inhibitors

scholarly journals Self-augmentation Effect of Male-specific Products on Sexually Differentiated Progesterone Metabolism in Adult Male Rat Liver Microsomes

2000 ◽  
Vol 276 (7) ◽  
pp. 4604-4610 ◽  
Author(s):  
Akihiko Yamada ◽  
Morio Yamada ◽  
Yukihisa Fujita ◽  
Takashi Nishigami ◽  
Keiji Nakasho ◽  
...  
Keyword(s):  
Rat Liver ◽  
Adult Male ◽  
Liver Microsomes ◽  
Male Rat ◽  
Rat Liver Microsomes ◽  
Progesterone Metabolism ◽  
Adult Male Rat ◽  
Male Specific

scholarly journals Progesterone-binding site of adult male rat liver microsomes.

1990 ◽  
Vol 265 (19) ◽  
pp. 11035-11043
Author(s):  
M Yamada ◽  
K Indo ◽  
T Nishigami ◽  
K Nakasho ◽  
H Miyaji
Keyword(s):  
Binding Site ◽  
Rat Liver ◽  
Adult Male ◽  
Liver Microsomes ◽  
Male Rat ◽  
Rat Liver Microsomes ◽  
Adult Male Rat

Relationship between Sigma-like site and progesterone-binding site of adult male rat liver microsomes

Hepatology ◽  
1994 ◽  
Vol 20 (5) ◽  
pp. 1271-1280 ◽  
Author(s):  
Morio Yamada ◽  
Takashi Nishigami ◽  
Keiji Nakasho ◽  
Yukiyasu Nishimoto ◽  
Hideki Miyaji
Keyword(s):  
Binding Site ◽  
Rat Liver ◽  
Adult Male ◽  
Liver Microsomes ◽  
Male Rat ◽  
Rat Liver Microsomes ◽  
Adult Male Rat

Oxidation of methyl- and ethyl- tertiary-butyl ethers in rat liver microsomes: role of the cytochrome P450 isoforms

1998 ◽  
Vol 72 (4) ◽  
pp. 207-214 ◽  
Author(s):  
Alessandra Turini ◽  
Giada Amato ◽  
Vincenzo Longo ◽  
Pier Giovanni Gervasi
Keyword(s):  
Cytochrome P450 ◽  
Rat Liver ◽  
Liver Microsomes ◽  
Rat Liver Microsomes ◽  
Tertiary Butyl ◽  
Cytochrome P450 Isoforms

Comprehensive Identification of Cytochrome P450 Isoforms from Solubility-Based Fractionated Rat Liver Microsomes

2007 ◽  
Vol 1 (4) ◽  
pp. 281-286 ◽  
Author(s):  
Hidenori Yamanaka ◽  
Masahiro Takeyoshi ◽  
Yasushi Minobe ◽  
Yoshikuni Yakabe ◽  
Mineo Takatsuki ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Rat Liver ◽  
Liver Microsomes ◽  
Rat Liver Microsomes ◽  
Cytochrome P450 Isoforms

STUDIES ON THE METABOLISM OF C19 STEROIDS IN RAT LIVER. 6. HYDROXYLATION OF 4-ANDROSTENE-3,17-DIONE IN RAT LIVER MICROSOMES

1970 ◽  
Vol 65 (1) ◽  
pp. 84-94 ◽  
Author(s):  
Jan-Åke Gustafsson ◽  
Belisário P. Lisboa
Keyword(s):  
Mass Spectrometry ◽  
Gas Chromatography ◽  
Rat Liver ◽  
Liver Microsomes ◽  
Gas Chromatography Mass Spectrometry ◽  
Male Rat ◽  
Rat Liver Microsomes ◽  
Relative Importance ◽  
Adult Male Rat ◽  
Layer Chromatography

ABSTRACT Following incubations of androstenedione with 105 000 × g microsomes of adult male rat liver, 6β-, 6α-, 7α-, 16α-, and 18-hydroxyandrostenedione were isolated by thin-layer chromatography and identified by gas chromatography-mass spectrometry. After incubations with testosterone the only 3,17-dioxo-Δ4-steroids formed were 6β- and 7α-hydroxyandrostenedione. 6β- and 18-Hydroxyandrostenedione were isolated after incubations with 6β- and 18-hydroxytestosterone, respectively. The relative importance of the 17-oxo- and the 17β-hydroxy-pathways in the formation of 3,17-dioxo-Δ4-C19O3 steroids is discussed.

scholarly journals Participation of two structurally related enzymes in rat hepatic microsomal androstenedione 7α-hydroxylation

1990 ◽  
Vol 265 (1) ◽  
pp. 187-194 ◽  
Author(s):  
D J Waxman ◽  
D P Lapenson ◽  
K Nagata ◽  
H D Conlon
Keyword(s):  
Rat Liver ◽  
Adult Female ◽  
Adult Male ◽  
Liver Microsomes ◽  
High Specificity ◽  
High Rate ◽  
Male Rat ◽  
Rat Liver Microsomes ◽  
Female Rat ◽  
Hydroxylase Activity

Rat hepatic cytochrome P-450 form 3 (testosterone 7 alpha-hydroxylase; P-450 gene IIA1) and P-450 form RLM2 (testosterone 15 alpha-hydroxylase; P-450 gene IIA2) are 88% identical in primary structure, yet they hydroxylate testosterone with distinct and apparently unrelated regioselectivities. In this study, androstenedione and progesterone were used to assess the regioselectivity and stereospecificity of these two P-450 enzymes towards other steroid substrates. Although P-450 RLM2 exhibited low 7 alpha-hydroxylase activity with testosterone or progesterone as substrate (turnover number less than or equal to 1-2 nmol of metabolite/min per nmol of P-450), it did catalyse androstenedione 7 alpha-hydroxylation at a high rate (21 min-1) which exceeded that of P-450 3 (7 min-1). However, whereas P-450 3 exhibited a high specificity for hydroxylation of these steroids at the 7 alpha position (95-97% of total activity), P-450 RLM2 actively metabolized these compounds at four or more major sites including the nearby C-15 position, which dominated in the case of testosterone and progesterone. The observation that androstenedione is actively 7 alpha-hydroxylated by purified P-450 RLM2 suggested that this P-450 enzyme might make significant contributions to microsomal androstenedione 7 alpha-hydroxylation, an activity that was previously reported to be associated with immunoreactive P-450 3. Antibody inhibition experiments were therefore carried out in liver microsomes using polyclonal anti-(P-450 3) antibodies which cross-react with P-450 RLM2, and using a monoclonal antibody that is reactive with and inhibitory towards P-450 3 but not P-450 RLM2. P-450 3 was thus shown to catalyse only around 35% of the total androstenedione 7 alpha-hydroxylase activity in uninduced adult male rat liver microsomes, with the balance attributed to P-450 RLM2. The P-450-3-dependent 7 alpha-hydroxylase activity was increased to approximately 65% of the total in phenobarbital-induced adult male microsomes, and to greater than 90% of the total in untreated adult female rat liver microsomes. These observations are consistent with the inducibility of P-450 3 by phenobarbital and with the absence of P-450 RLM2 from adult female rat liver respectively. These findings establish that P-450 RLM2 and P-450 3 can both contribute significantly to microsomal androstenedione 7 alpha-hydroxylation, thus demonstrating that the 7 alpha-hydroxylation of this androgen does not serve as a specific catalytic monitor for microsomal P-450 3.

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