Center for Bioinformatics
Oxidoreductases | Transferases | Hydrolases | Lyases | Isomerases | Ligases

Basic Information

Enzyme Number

1.1.1.34

Official Name

hydroxymethylglutaryl-CoA reductase (NADPH)

Name from literature

3-hydroxy-methylglutaryl coenzyme A

Pathway from literature

cholesterol synthesis/the isoprenoid biosynthetic pathway

Pathway from KEGG

Lipid Metabolism; Biosynthesis of steroids; map00100

Organisms

Human (9606)

Genome localization

5q13.3-q14[3156 ],

Comments

The enzyme is inactivated by EC 2.7.11.31 {[hydroxymethylglutaryl-CoA reductase (NADPH)] kinase} and reactivated by EC 3.1.3.47 {[hydroxymethylglutaryl-CoA reductase (NADPH)]-phosphatase}.

Rate-limiting Description

"HMGCR catalyzes the rate-limiting step in cholesterol biosynthesis, and also plays a significant role in cholesterol homeostasis." (18815589)

Regulatory Information

Upstream transcription factor

6720;3091

Regulatory type

Detail

key enzyme;

"HMG CoA reductase inhibitors (""statins""), which inhibit a key enzyme in the mevalonate pathway, are widely used for the treatment of hyperlipidemia." (9558731#12736772)

transcriptional level;

"characterization of the coordinated regulation of cholesterol metabolism in human liver; regulation of its mRNA in liver" (12213890)

inhibitor;

"Competitive inhibitors of the reductase induce the expression of LDL receptors in the liver, which in turn increases the catabolism of plasma LDL and lowers the plasma concentration of cholesterol, an important determinant of atherosclerosis." (15811249)

transcriptional level;neuregulin-1

"In Schwann cells neuregulin-1 increases the transcription of the 3-hydroxy-3-methylglutarylcoenzyme A reductase, the rate-limiting enzyme for cholesterol biosynthesis." (17652086)

transcriptional factor;SREBP(6720)

"The roles of sterol regulatory element-binding protein (SREBP)-dependent gene expression, side chain oxysterol biosynthesis, and cholesterol precursors in the short term regulation of endoplasmic reticulum cholesterol level and HMGR activity, is examined." (18024962)

transcriptional factor;HIF-1alpha(3091),SREBP2

"HIF-1alpha accumulation is able to increase level and activity of HMG-CoAR by stimulating its transcription.#The raised transcription of the reductase could be related to an induction by HIF-1alpha even if a parallel action of SREBP-2 actively translocated to nucleus by the increased level of SCAP cannot be excluded." (18459144)

phosphorylation;

P04035

Gene ontology

Gene ontology

GO:0050661 (F) NADP binding [P04035 ];
GO:0008299 (P) isoprenoid biosynthetic process [P04035 ];
GO:0008406 (P) gonad development [P04035 ];
GO:0005778 (C) peroxisomal membrane [P04035 ];
GO:0008354 (P) germ cell migration [P04035 ];
GO:0006695 (P) cholesterol biosynthetic process [P04035 ];
GO:0005789 (C) endoplasmic reticulum membrane [P04035 ];
GO:0015936 (P) coenzyme A metabolic process [P04035 ];
GO:0016021 (C) integral to membrane [P04035 ];
GO:0004420 (F) hydroxymethylglutaryl-CoA reductase (NADPH)... [P04035 ];
GO:0055114 (P) oxidation reduction [P04035 ];

Subcellular localization

Localization

endoplasmic reticulum [P04035 ];

peroxisome [P04035 ];

Links

SwissProt

P04035

Entrez Gene

3156

HPRD

00836



  Copyright 2009, Center for Bioinformatics 
  Last Modified: 2009-03-24  
  Design by Zhao Min