Schwartzman M L, Martasek P, Rios A R, Levere R D, Solangi K, Goodman A I, Abraham N G
Department of Medicine, New York Medical College, Valhalla.
Kidney Int. 1990 Jan;37(1):94-9. doi: 10.1038/ki.1990.13.
Cytochrome P450-dependent arachidonic acid metabolism in human kidney cortex from several postmortem subjects has been characterized. Using HPLC and GC/MS, four cytochrome P450-arachidonic acid metabolites were tentatively but not unequivocally identified as epoxyeicosatrienoic acid (EET), dihydroxyeicosatrienoic acid (DHT) and 19- and 20-hydroxyeicosatetraenoic acids, suggesting the involvement of two major cytochrome P450 enzymes, epoxygenase and omega/omega-1 hydroxylases. This pattern of metabolism was similar to that found in rabbit and rat kidneys. The formation of these metabolites was dependent on the presence of NADPH and inhibited by IgG of NADPH-cytochrome P450 (c) reductase. Immunologic studies of renal cytochrome P450 epoxygenase demonstrated that antibodies prepared against human-purified hepatic cytochrome P450 epoxygenase recognized renal enzyme protein and inhibited the enzyme activity by 92%. In contrast, control immunoglobulin did not inhibit renal cytochrome P450 epoxygenase. Antibody inhibition of renal cytochrome P450 epoxygenase demonstrated a degree of conservation of both enzyme proteins between liver and kidney. Antibodies against lauric acid omega/omega-1 hydroxylases (P450 omega) inhibited the formation of omega/omega-1 hydroxylase products, 19- and 20-HETEs. Identical qualitative patterns of arachidonic acid metabolites were observed in all cortical microsomes studied. Interindividual variations were observed in the cytochrome P450-dependent arachidonic acid metabolism, and the activities ranged from 0.031 to 5.027 nmol arachidonic acid converted/mg protein/30 min. which is about a 150-fold difference. However, when the specific activities for total cytochrome P450-dependent arachidonic acid metabolism were calculated, two separate groups could be distinguished, high and low metabolizers of arachidonic acid.(ABSTRACT TRUNCATED AT 250 WORDS)
已对来自数名尸检对象的人肾皮质中细胞色素P450依赖性花生四烯酸代谢进行了表征。使用高效液相色谱法（HPLC）和气相色谱 - 质谱联用仪（GC/MS），初步但未明确鉴定出四种细胞色素P450 - 花生四烯酸代谢产物为环氧二十碳三烯酸（EET）、二羟基二十碳三烯酸（DHT）以及19 - 和20 - 羟基二十碳四烯酸，这表明有两种主要的细胞色素P450酶参与其中，即环氧化酶和ω/ω - 1羟化酶。这种代谢模式与在兔和大鼠肾脏中发现的相似。这些代谢产物的形成依赖于烟酰胺腺嘌呤二核苷酸磷酸（NADPH）的存在，并受到NADPH - 细胞色素P450（c）还原酶的IgG抑制。对肾细胞色素P450环氧化酶的免疫学研究表明，针对人纯化的肝细胞色素P450环氧化酶制备的抗体能够识别肾酶蛋白，并将酶活性抑制92%。相比之下，对照免疫球蛋白并未抑制肾细胞色素P450环氧化酶。肾细胞色素P450环氧化酶的抗体抑制表明肝脏和肾脏之间两种酶蛋白存在一定程度的保守性。针对月桂酸ω/ω - 1羟化酶（P450ω）的抗体抑制了ω/ω - 1羟化酶产物19 - 和20 - 羟基二十碳四烯酸（HETEs）的形成。在所研究的所有皮质微粒体中均观察到相同的花生四烯酸代谢产物定性模式。在细胞色素P450依赖性花生四烯酸代谢中观察到个体间差异，活性范围为0.031至5.027 nmol花生四烯酸转化/mg蛋白质/30分钟，相差约150倍。然而，当计算总细胞色素P450依赖性花生四烯酸代谢的比活性时，可以区分出两个不同的组，即花生四烯酸的高代谢者和低代谢者。（摘要截断于250字）
