羟甲基戊二酸单酰辅酶A还原酶

  此條目介紹的是NAD+为受体的酶。关于同名但以NADP+为受体的酶，请见「羟甲基戊二酸单酰辅酶A还原酶 (NADPH)」。
3-羟-3-甲基戊二酰辅酶A还原酶
PDB rendering based on 1dq8.
有效结构
PDB 直系同源检索：PDBe, RCSB
标识
代号 HMGCR; LDLCQ3
扩展标识 遗传学：142910 鼠基因：96159 同源基因：30994 ChEMBL: 402 GeneCards: HMGCR Gene
EC編號 1.1.1.34
RNA表达模式
更多表达数据
直系同源体
物种 人类 小鼠
Entrez 3156 15357
Ensembl ENSG00000113161 ENSMUSG00000021670
UniProt P04035 E9PVG9
mRNA序列 NM_000859.2 NM_008255.2
蛋白序列 NP_000850.1 NP_032281.2
基因位置 Chr 5:
74.63 – 74.66 Mb		 Chr 13:
97.42 – 97.44 Mb
PubMed查询 [1] [2]
羟甲基戊二酸单酰辅酶A还原酶
识别码
EC編號 1.1.1.88
CAS号 37250-24-1
数据库
IntEnz IntEnz浏览
BRENDA（英语：BRENDA） BRENDA入口
ExPASy（英语：ExPASy） NiceZyme浏览
KEGG KEGG入口
MetaCyc（英语：MetaCyc） 代谢路径
PRIAM（英语：PRIAM_enzyme-specific_profiles） 概述
PDB RCSB PDB PDBj PDBe PDBsum
基因本体 AmiGO / EGO

羟甲基戊二酸单酰辅酶A还原酶（英語：hydroxymethylglutaryl-CoA reductase，EC 1.1.1.88 （页面存档备份，存于互联网档案馆））简称“HMG-CoA还原酶”，是一种以NAD+或NADP+为受体、作用于供体CH-OH基团上的氧化还原酶。这种酶能催化以下酶促反应：

(R)-甲羟戊酸 + 辅酶A + 2 NAD+ 3-羟基-3-甲基戊二酸单酰辅酶A + 2 NADH + 2 H+

HMG-CoA还原酶是产生胆固醇等类异戊二烯化合物的甲羟戊酸代谢途径中的限速酶。一般来说，在哺乳动物细胞中HMG-CoA还原酶受到由低密度脂蛋白受体内化及降解低密度脂蛋白产生的胆固醇及胆固醇的氧化衍生物的抑制。低密度脂蛋白是动脉粥样硬化的一个决定性因素，这种酶的竞争性抑制剂能诱导肝脏低密度脂蛋白受体的表达，使细胞质基质内低密度脂蛋白的代谢增强、浓度降低。[1]因此，HMG-CoA还原酶成为被统称为“羟甲基戊二酸单酰辅酶A还原酶抑制剂”的一类被广泛使用的降胆固醇药的作用靶点。HMG-CoA被锚定在内质网膜上，且长期以来被认为拥有7个跨膜结构域，而其活性位点则位于蛋白质C端结构域中。但后来的研究表明HMG-CoA还原酶其实拥有8个跨膜结构域。[2]

人类表达HMG-CoA还原酶的基因位于5号染色体长臂上（5q13.3-14）。[3]其他动物、植物和细菌也拥有具有类似作用的相关酶类。

反应

在甲羟戊酸途径中，HMG-CoA还原酶负责将3-羟基-3-甲基戊二酸单酰辅酶A（HMG-CoA）催化转化为甲羟戊酸:

甲羟戊酸途径示意图

参考文献

  1. ^ Entrez Gene: HMGCR 3-hydroxy-3-methylglutaryl-Coenzyme A reductase. （原始内容存档于2010-03-07）. 
  2. ^ Roitelman J, Olender EH, Bar-Nun S, Dunn WA, Simoni RD. Immunological evidence for eight spans in the membrane domain of 3-hydroxy-3-methylglutaryl coenzyme A reductase: implications for enzyme degradation in the endoplasmic reticulum. J. Cell Biol. June 1992, 117 (5): 959–73. PMC 2289486 可免费查阅. PMID 1374417. doi:10.1083/jcb.117.5.959. 
  3. ^ Lindgren V, Luskey KL, Russell DW, Francke U. Human genes involved in cholesterol metabolism: chromosomal mapping of the loci for the low density lipoprotein receptor and 3-hydroxy-3-methylglutaryl-coenzyme A reductase with cDNA probes. Proc. Natl. Acad. Sci. U.S.A. December 1985, 82 (24): 8567–71. PMC 390958 可免费查阅. PMID 3866240. doi:10.1073/pnas.82.24.8567. 
  • Fimognari, G.M. and Rodwell, V.W. Substrate-competitive inhibition of bacterial mevalonate:nicotinamide-adenine dinucleotide oxidoreductase (acylating CoA). Biochemistry. 1965, 4: 2086–2090. 

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