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硬脂酰辅酶A去饱和酶的调控及其在代谢中的作用。

Regulation of stearoyl-CoA desaturases and role in metabolism.

作者信息

Ntambi James M, Miyazaki Makoto

机构信息

Department of Biochemistry, University of Wisconsin, 433 Babcock Drive, Madison, WI 53706, USA.

出版信息

Prog Lipid Res. 2004 Mar;43(2):91-104. doi: 10.1016/s0163-7827(03)00039-0.

DOI:10.1016/s0163-7827(03)00039-0
PMID:14654089
Abstract

Stearoyl-CoA desaturase (SCD) is the rate-limiting enzyme catalyzing the synthesis of monounsaturated fatty acids, mainly oleate (18:1) and palmitoleate (16:1). These represent the major monounsaturated fatty acids of membrane phospholipids, triglycerides, wax esters and cholesterol esters. The ratio of saturated to monounsaturated fatty acids affects phospholipid composition and alteration in this ratio has been implicated in a variety of disease states including cardiovascular disease, obesity, diabetes, neurological disease, and cancer. For this reason, the expression of SCD is of physiological significance in both normal and disease states. Several SCD gene isoforms (SCD1, SCD2, SCD3) exist in the mouse and one SCD isoform that is highly homologous to the mouse SCD1 is well characterized in human. The physiological role of each SCD isoform and the reason for having three or more SCD gene isoforms in the rodent genome are currently unknown but could be related the substrate specificities of the isomers and their regulation through tissue-specific expression. The recent studies of asebia mouse strains that have a natural mutation in the SCD1 gene and a mouse model with a targeted disruption of the SCD1 gene have provided clues concerning the role that SCD1 and its endogenous products play in the regulation of metabolism.

摘要

硬脂酰辅酶A去饱和酶(SCD)是催化单不饱和脂肪酸合成的限速酶,主要合成油酸(18:1)和棕榈油酸(16:1)。这些是膜磷脂、甘油三酯、蜡酯和胆固醇酯的主要单不饱和脂肪酸。饱和脂肪酸与单不饱和脂肪酸的比例会影响磷脂组成,而该比例的改变与多种疾病状态有关,包括心血管疾病、肥胖症、糖尿病、神经疾病和癌症。因此,SCD的表达在正常和疾病状态下均具有生理意义。小鼠体内存在几种SCD基因亚型(SCD1、SCD2、SCD3),在人类中已对一种与小鼠SCD1高度同源的SCD亚型进行了充分表征。目前尚不清楚每种SCD亚型的生理作用以及啮齿动物基因组中存在三种或更多SCD基因亚型的原因,但这可能与异构体的底物特异性及其通过组织特异性表达的调控有关。最近对SCD1基因发生自然突变的无毛小鼠品系以及SCD1基因靶向敲除的小鼠模型的研究,为SCD1及其内源性产物在代谢调节中所起的作用提供了线索。

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