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人类II型精氨酸酶基因的克隆与特性分析

Cloning and characterization of the human type II arginase gene.

作者信息

Vockley J G, Jenkinson C P, Shukla H, Kern R M, Grody W W, Cederbaum S D

机构信息

Department of Molecular Diagnostics, SmithKline Pharmaceuticals, King of Prussia, Pennsylvania 19406, USA.

出版信息

Genomics. 1996 Dec 1;38(2):118-23. doi: 10.1006/geno.1996.0606.

Abstract

There are two forms of arginase in humans, both catalyzing the hydrolysis of arginine to ornithine and urea. Recent studies in animal models and in Type I arginase-deficient patients suggest that Type II arginase is inducible and may play an important role in the regulation of extra-urea cycle arginine metabolism by modulating cellular arginine concentrations. We PCR amplified and cloned the human Type II arginase gene, the first nonliver arginase gene reported in mammals. While sequence homology to Type I arginase, arginase activity data, and immunoprecipitation with an anti-AII antibody confirm the identity of this gene, Northern blot analysis demonstrates its differential expression in the brain, prostate, and kidney. Type II arginase may be an important part of the arginine regulatory system affecting nitric oxide synthase, arginine decarboxylase, kyotorphin synthase, and arginine-glycine transaminase activities and polyamine and proline biosynthesis.

摘要

人类体内有两种形式的精氨酸酶,二者均可催化精氨酸水解生成鸟氨酸和尿素。近期针对动物模型及I型精氨酸酶缺乏症患者的研究表明,II型精氨酸酶具有诱导性,可能通过调节细胞内精氨酸浓度,在尿素循环外的精氨酸代谢调节中发挥重要作用。我们通过聚合酶链反应(PCR)扩增并克隆了人类II型精氨酸酶基因,这是哺乳动物中首个报道的非肝脏来源的精氨酸酶基因。虽然该基因与I型精氨酸酶的序列同源性、精氨酸酶活性数据以及用抗II型精氨酸酶抗体进行的免疫沉淀结果均证实了该基因的身份,但Northern印迹分析表明其在脑、前列腺和肾脏中存在差异表达。II型精氨酸酶可能是精氨酸调节系统的重要组成部分,影响一氧化氮合酶、精氨酸脱羧酶、脑啡肽合成酶以及精氨酸-甘氨酸转氨酶的活性,以及多胺和脯氨酸的生物合成。

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