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hydroxymethylglutaryl [HMG] CoA reductase (HMGCR)
Function:
- regulation of cholesterol biosynthesis
- rate-limiting enzyme of sterol biosynthesis
- metabolic intermediate biosynthesis
- mevalonate biosynthesis
- R-mevalonate from acetyl-CoA: step 3/3
- HMG CoA reductase activity is regulated at 3 levels:
a) transcriptional (8 fold)
b) translational (5 fold)
c) proteolytic (5 fold)
- regulation is affected by sterols (transcriptional & proteolytic) derived from LDL & non-sterol molecule(s) derived from mevalonate (translational & proteolytic) [2].
(R)-mevalonate + CoA + 2 NADP+ .
(S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADPH
Inhibition:
- inhibited by statins
Structure:
- homodimer
- belongs to the HMG-CoA reductase family
Compartment:
- endoplasmic reticulum membrane
- peroxisome membrane
Alternative splicing: named isoforms=2
Laboratory:
- HMG CoA reductase Ab in serum
- HMG CoA reductase IgG in serum
Interactions
molecular events
Related
cholesterol biosynthesis
HMG CoA reductase gene
HMG CoA reductase inhibitor (statin)
General
glycoprotein
oxidoreductase
transmembrane 7 protein
Properties
SIZE: entity length = 888 aa
MW = 97 kD
COMPARTMENT: peroxisome
endoplasmic reticulum
MOTIF: transmembrane domain {10-39}
transmembrane domain {57-78}
transmembrane domain {90-114}
transmembrane domain {124-149}
transmembrane domain {160-187}
transmembrane domain {192-220}
N-glycosylation site {N281}
N-glycosylation site {N296}
transmembrane domain {315-339}
Linker {340-449}
MOTIF: N-glycosylation site {N419}
active site
SITE: 450-888
MOTIF: N-glycosylation site {N518}
glutamate residue {E559}
lysine residue {K691}
aspartate residue {D767}
histidine residue {H866}
N-glycosylation site {N870}
MISC-INFO: 1/2life 2-3 HOURS
INHIBITOR = CHOLESTEROL
Database Correlations
OMIM 142910
UniProt P04035
Pfam PF00368
KEGG correlations
ENZYME correlations
References
- Primary Hyperlipoproteinemias, Steiner & Shafrir (eds),
McGraw Hill, NY, 1991, pg 14
- Goldstein JL, Brown MS.
Regulation of the mevalonate pathway.
Nature. 1990 Feb 1;343(6257):425-30. Review.
PMID: 1967820
- UniProt :accession P04035