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

Basic Information

Enzyme Number

Official Name

hydroxymethylglutaryl-CoA synthase

Name from literature

HMG CoA synthase

Pathway from literature

mevalonate pathway/ketogenesis

Pathway from KEGG

Amino Acid Metabolism; Valine, leucine and isoleucine degradation; map00280

Lipid Metabolism; Synthesis and degradation of ketone bodies; map00072

Carbohydrate Metabolism; Butanoate metabolism; map00650


Human (9606)

Genome localization

1p13-p12[3158 ], 5p14-p13[3157 ],

Rate-limiting Description

"The mode of action of these compounds in the 50-100 microM concentration range appeared to be by increasing lipid excretion from the body and by inhibiting rate-limiting enzyme activities for the de novo synthesis of lipids and cholesterol (e.g., phosphatidylate phosphohydrolase, ATP-dependent citrate lyase, cytoplasmic acetyl coenzyme A ." (CoA synthetase, HMG CoA reductase, and acetyl CoA carboxylase))

Regulatory Information

Upstream transcription factor


Regulatory type


key enzyme;

"Statins operate through inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, a key enzyme which regulates intracellular cholesterol synthesis." (15518071)

transcriptional factor;SREBP(6720)

"The changes in gene expression were followed by enhanced HMGCR-enzyme activity and elevated cellular levels of cholesterol and triglycerides. The upregulated genes are all known to be controlled by the sterol regulatory element-binding protein (SREBP) transcription factors.#Antidepressant drugs activate SREBP and up-regulate cholesterol and fatty acid biosynthesis in human glial cells." (16027736#16324787)

transcriptional factor;c-myc(4609)

"Ketogenesis is an undesirable metabolic characteristic of the proliferating cell, which is down-regulated through c-Myc-mediated repression of the key metabolic gene HMGCS2." (16940161)


"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." (17081983)









Gene ontology

Gene ontology

GO:0008299 (P) isoprenoid biosynthetic process [Q01581, P54868 ];
GO:0005625 (C) soluble fraction [Q01581 ];
GO:0005759 (C) mitochondrial matrix [P54868 ];
GO:0005829 (C) cytosol [Q01581 ];
GO:0004421 (F) hydroxymethylglutaryl-CoA synthase activity [Q01581, P54868 ];
GO:0006695 (P) cholesterol biosynthetic process [Q01581, P54868 ];

Tissue expression

Tissue From HPRD

Heart [02580 ];
Colon [02580 ];
Testis [02580 ];
Liver [02580 ];
Kidney [02580 ];
Muscle [02580 ];
Fetus [07515 ];

Tissue specificity

Liver and kidney [P54868 ];

Subcellular localization


mitochondrion [P54868 ];

cytoplasm [Q01581 ];

Disease relevance


Defects in HMGCS2 are the cause of HMG-CoA synthase deficiency [MIM:605911];
also known as deficiency of mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase 2. Affected individuals present with severe hypoketotic hypoglycemia, mild hepatomegaly, or fatty liver, and a nondiagnostic pattern of urinary organic acids with increase of medium and short chain dicarboxylic acids [P54868 ];



P54868; Q01581

Entrez Gene

3157; 3158


07515; 02580

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