Abstract：
:Rat hepatic microsomes catalyzed the formation of two distinct glutathione conjugates of bilirubin dimethylester (DMB). The two conjugates were identical to those isolated from the bile of Gunn rats infused with DMB. The microsomal reaction was dependent on NADPH, oxygen and glutathione and was inhibited by nitrogen and the cytochrome P450 inhibitors metyrapone, 1-benzyl-imidazole, and alpha-naphthoflavone. Conjugate formation was inducible with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) but not phenobarbital pretreatment. The rate of formation of conjugates was not affected by washings of the microsomal pellet or by the presence of superoxide dismutase and/or catalase. Cation fast atom bombardment mass spectrometry (FAB/MS) of the conjugates indicated a molecular ion of 937 atomic mass units (amu). Fragmentation revealed a loss of 307 amu, consistent with glutathione, and a residual mass of 629 amu suggesting a hydroxylated derivative of DMB (612 amu). Cation FAB/MS/MS of conjugates formed in vitro under an atmosphere of oxygen-16 and oxygen-18 demonstrated the incorporation of molecular oxygen by a difference of 2 amu in the respective molecular ions. Our results suggest that DMB is oxidized by the cytochrome P450 IA gene family to an epoxide intermediate which is then subsequently conjugated with glutathione.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Shore LJ,Mogilevsky WS,Smith PB,Fenselau C,Odell GBdoi
10.1016/0006-2952(91)90597-xsubject
Has Abstractpub_date
1991-10-24 00:00:00pages
1969-76issue
10eissn
0006-2952issn
1873-2968pii
0006-2952(91)90597-Xjournal_volume
42pub_type
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pub_type： 杂志文章
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更新日期：2004-05-01 00:00:00
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更新日期：1990-11-01 00:00:00
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