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

Rat (10116)

Genome localization

2q12[25675 ],

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

"The rate-limiting enzymes of cholesterol (HMG CoA reductase) and ceramide (serine palmitoyl transferase) synthesis were not affected." (10084306)

"Toxicological evaluation was performed in serum samples following the administration of the therapeutic dose regimens of the compounds that were previously shown to be effective in inhibition of 3-hydroxy-methylglutaryl coenzyme A (HMG CoA) reductase, the enzyme controlling the rate-limiting step in the synthesis of cholesterol, and acyl-CoA cholesterol acyl transferase (ACAT) which converts intracellular free cholesterol to cholesterol ester." (10204089)

Regulatory Information

Upstream transcription factor

81646;300095

Regulatory type

Detail

phosphorylation;

P51639

phosphorylation;

P51639:from_uniprot:871_Phosphoserine

transcriptional factor;CREB(81646)

"Deletion of the region containing the cyclic AMP response element (CRE) at -104 to -96 and an NF-Y site at -70 to -65 resulted in marked reduction of promoter activity." (17327468)

phosphorylation;

"Reactive oxygen species effect on the HMG-CoAR dephosphorylation is mediated by the activation of p38/MAPK pathway." (18031790)

transcriptional factor;SREBP-2(300095)

"In CRF rats, a twofold increase in SREBP-2 mRNA level, as well as in mature SREBP-2 protein abundance was found, when compared to control animals. It was associated with enhanced activity and mRNA abundance of liver HMG-CoA reductase, a rate-limiting enzyme for cholesterol biosynthesis." (16814791)

Gene ontology

Gene ontology

GO:0050661 (F) NADP binding [P51639 ];
GO:0015936 (P) coenzyme A metabolic process [P51639 ];
GO:0008299 (P) isoprenoid biosynthetic process [P51639 ];
GO:0016021 (C) integral to membrane [P51639 ];
GO:0004420 (F) hydroxymethylglutaryl-CoA reductase (NADPH)... [P51639 ];
GO:0055114 (P) oxidation reduction [P51639 ];
GO:0006695 (P) cholesterol biosynthetic process [P51639 ];
GO:0005789 (C) endoplasmic reticulum membrane [P51639 ];

Subcellular localization

Localization

endoplasmic reticulum [P51639 ];

Links

SwissProt

P51639

Entrez Gene

25675



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  Last Modified: 2009-03-24  
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