Leithauser M T, Roerig D L, Winquist S M, Gee A, Okita R T, Masters B S
Department of Biochemistry, Medical College of Wisconsin, Milwaukee 53226.
Prostaglandins. 1988 Dec;36(6):819-33. doi: 10.1016/0090-6980(88)90059-7.
Cytochrome P450PG omega is induced in the rabbit lung in a gestational age-dependent manner and hydroxylates certain eicosanoids at their terminal, or omega (omega), carbon. This enzyme has been isolated from microsomal fractions and its activity has been characterized (Williams, D.E., et al., J. Biol. Chem. 259; 14600-14608, 1984). The experiments presented here examine the omega-hydroxylation activity of the intact lung during presentation of an eicosanoid substrate, prostaglandin E1 (PGE1), to the lung vasculature. Isolated, perfused lungs from three pregnant and four nonpregnant rabbits were injected with [3H]-PGE1. One-second fractions were collected from the perfusion effluent and were analyzed for metabolism of PGE1. Lungs isolated from pregnant rabbits metabolized PGE1 mainly to two polar derivatives, 20-hydroxy-PGE1 and 13,14-dihydro-15-keto-20-hydroxy-PGE1, whereas lungs from nonpregnant rabbits yielded mainly a relatively nonpolar metabolite, 13,14-dihydro-15-keto-PGE1. These metabolites were identified by coelution with standards that were generated enzymatically in vitro and whose structures were confirmed by gas chromatography/mass spectrometry (GC/MS).
细胞色素P450PGω在兔肺中以依赖胎龄的方式被诱导，并且在某些类二十烷酸的末端或ω（Ω）碳原子处使其羟基化。这种酶已从微粒体组分中分离出来，其活性也已有相关描述（威廉姆斯，D.E.等人，《生物化学杂志》259卷；14600 - 14608页，1984年）。此处呈现的实验研究了在向肺血管系统提供类二十烷酸底物前列腺素E1（PGE1）时，完整肺脏的ω - 羟基化活性。给三只怀孕兔子和四只未怀孕兔子的离体灌注肺脏注射[3H] - PGE1。从灌注流出物中收集1秒的组分，并分析PGE1的代谢情况。从怀孕兔子分离出的肺脏将PGE1主要代谢为两种极性衍生物，即20 - 羟基 - PGE1和13,14 - 二氢 - 15 - 酮 - 20 - 羟基 - PGE1，而从未怀孕兔子分离出的肺脏主要产生一种相对非极性的代谢物，即13,14 - 二氢 - 15 - 酮 - PGE1。这些代谢物通过与体外酶促生成的标准品共洗脱来鉴定，其结构通过气相色谱/质谱联用仪（GC/MS）得以确认。
