HMG-CoA Reductase

Supporting information

3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA reductase) catalyzes the rate limiting step in cholesterol biosynthesis - the conversion of 3-hydroxy-3-methyl-glutaryl-CoA into mevalonic acid. This transmembrane enzyme is bound to the endoplasmic reticulum and is ubiquitously expressed.

When cholesterol levels falls, HMG-CoA reductase is transcriptionally upregulated by sterol regulatory element binding protein (SREBP), which binds to the sterol regulatory element (SRE) in the 5' region of the HMG-CoA gene. When cholesterol levels are elevated, short-term regulation of HMG-CoA is mediated by Ser872 phosphorylation by AMP-activated protein kinase and long-term regulation is mediated by the increased sensitivity of this enzyme to proteolytic breakdown. HMG-CoA reductase is the pharmalogical target for statins and the human gene encoding this enzyme is localized to 5q13.3-q14.

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Species Gene Symbol Gene Accession No. Protein Accession No.
Human HMGCR NM_000859 P04035
Mouse Hmgcr NM_008255 Q01237
Rat Hmgcr NM_013134 P51639

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