HMGCR

From Wikipedia, the free encyclopedia

3-hydroxy-3-methylglutaryl-Coenzyme A reductase

PDB rendering based on 1dq8.

Available structures: 1dq8, 1dq9, 1dqa, 1hw8, 1hw9, 1hwi, 1hwj, 1hwk, 1hwl

Identifiers

Symbol(s)

HMGCR;

External IDs

OMIM: 142910 MGI: 96159 HomoloGene: 30994

Gene ontology
Molecular Function:	• hydroxymethylglutaryl-CoA reductase (NADPH) activity • oxidoreductase activity
Cellular Component:	• membrane fraction • peroxisome • endoplasmic reticulum • endoplasmic reticulum membrane • microsome • membrane • integral to membrane
Biological Process:	• lipid metabolic process • cholesterol biosynthetic process • germ cell migration • gonad development • embryonic development

RNA expression pattern

More reference expression data

Orthologs

Human

Mouse

Refseq

NM_000859 (mRNA)
NP_000850 (protein)

NM_008255 (mRNA)
NP_032281 (protein)

Location

Chr 5: 74.67 - 74.69 Mb

Chr 13: 97.75 - 97.77 Mb

Pubmed search

[1]

[2]

3-hydroxy-3-methylglutaryl-Coenzyme A reductase, also known as HMGCR, is a human gene.

HMG-CoA reductase is the rate-limiting enzyme for cholesterol synthesis and is regulated via a negative feedback mechanism mediated by sterols and non-sterol metabolites derived from mevalonate, the product of the reaction catalyzed by reductase. Normally in mammalian cells this enzyme is suppressed by cholesterol derived from the internalization and degradation of low density lipoprotein (LDL) via the LDL receptor. 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.^[1]

[edit] References

^ Entrez Gene: HMGCR 3-hydroxy-3-methylglutaryl-Coenzyme A reductase.

[edit] Further reading

Hodge VJ, Gould SJ, Subramani S, et al. (1992). "Normal cholesterol synthesis in human cells requires functional peroxisomes.". Biochem. Biophys. Res. Commun. 181 (2): 537–41. PMID 1755834.
Ramharack R, Tam SP, Deeley RG (1991). "Characterization of three distinct size classes of human 3-hydroxy-3-methylglutaryl coenzyme A reductase mRNA: expression of the transcripts in hepatic and nonhepatic cells.". DNA Cell Biol. 9 (9): 677–90. PMID 1979742.
Clarke PR, Hardie DG (1990). "Regulation of HMG-CoA reductase: identification of the site phosphorylated by the AMP-activated protein kinase in vitro and in intact rat liver.". EMBO J. 9 (8): 2439–46. PMID 2369897.
Luskey KL, Stevens B (1985). "Human 3-hydroxy-3-methylglutaryl coenzyme A reductase. Conserved domains responsible for catalytic activity and sterol-regulated degradation.". J. Biol. Chem. 260 (18): 10271–7. PMID 2991281.
Humphries SE, Tata F, Henry I, et al. (1986). "The isolation, characterisation, and chromosomal assignment of the gene for human 3-hydroxy-3-methylglutaryl coenzyme A reductase, (HMG-CoA reductase).". Hum. Genet. 71 (3): 254–8. PMID 2998972.
Beg ZH, Stonik JA, Brewer HB (1987). "Phosphorylation and modulation of the enzymic activity of native and protease-cleaved purified hepatic 3-hydroxy-3-methylglutaryl-coenzyme A reductase by a calcium/calmodulin-dependent protein kinase.". J. Biol. Chem. 262 (27): 13228–40. PMID 3308873.
Osborne TF, Goldstein JL, Brown MS (1985). "5' end of HMG CoA reductase gene contains sequences responsible for cholesterol-mediated inhibition of transcription.". Cell 42 (1): 203–12. PMID 3860301.
Lindgren V, Luskey KL, Russell DW, Francke U (1986). "Human genes involved in cholesterol metabolism: chromosomal mapping of the loci for the low density lipoprotein receptor and 3-hydroxy-3-methylglutaryl-coenzyme A reductase with cDNA probes.". Proc. Natl. Acad. Sci. U.S.A. 82 (24): 8567–71. PMID 3866240.
Lehoux JG, Kandalaft N, Belisle S, Bellabarba D (1985). "Characterization of 3-hydroxy-3-methylglutaryl coenzyme A reductase in human adrenal cortex.". Endocrinology 117 (4): 1462–8. PMID 3896758.
Boguslawski W, Sokolowski W (1984). "HMG-CoA reductase activity in the microsomal fraction from human placenta in early and term pregnancy.". Int. J. Biochem. 16 (9): 1023–6. PMID 6479432.
Harwood HJ, Schneider M, Stacpoole PW (1984). "Measurement of human leukocyte microsomal HMG-CoA reductase activity.". J. Lipid Res. 25 (9): 967–78. PMID 6491541.
Nguyen LB, Salen G, Shefer S, et al. (1994). "Deficient ileal 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in sitosterolemia: sitosterol is not a feedback inhibitor of intestinal cholesterol biosynthesis.". Metab. Clin. Exp. 43 (7): 855–9. PMID 8028508.
Bennis F, Favre G, Le Gaillard F, Soula G (1993). "Importance of mevalonate-derived products in the control of HMG-CoA reductase activity and growth of human lung adenocarcinoma cell line A549.". Int. J. Cancer 55 (4): 640–5. PMID 8406993.
Van Doren M, Broihier HT, Moore LA, Lehmann R (1998). "HMG-CoA reductase guides migrating primordial germ cells.". Nature 396 (6710): 466–9. doi:10.1038/24871. PMID 9853754.
Cargill M, Altshuler D, Ireland J, et al. (1999). "Characterization of single-nucleotide polymorphisms in coding regions of human genes.". Nat. Genet. 22 (3): 231–8. doi:10.1038/10290. PMID 10391209.
Aboushadi N, Engfelt WH, Paton VG, Krisans SK (1999). "Role of peroxisomes in isoprenoid biosynthesis.". J. Histochem. Cytochem. 47 (9): 1127–32. PMID 10449533.
Honda A, Salen G, Honda M, et al. (2000). "3-Hydroxy-3-methylglutaryl-coenzyme A reductase activity is inhibited by cholesterol and up-regulated by sitosterol in sitosterolemic fibroblasts.". J. Lab. Clin. Med. 135 (2): 174–9. doi:10.1067/mlc.2000.104459. PMID 10695663.
Istvan ES, Palnitkar M, Buchanan SK, Deisenhofer J (2000). "Crystal structure of the catalytic portion of human HMG-CoA reductase: insights into regulation of activity and catalysis.". EMBO J. 19 (5): 819–30. doi:10.1093/emboj/19.5.819. PMID 10698924.
Istvan ES, Deisenhofer J (2001). "Structural mechanism for statin inhibition of HMG-CoA reductase.". Science 292 (5519): 1160–4. doi:10.1126/science.1059344. PMID 11349148.
Rasmussen LM, Hansen PR, Nabipour MT, et al. (2002). "Diverse effects of inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase on the expression of VCAM-1 and E-selectin in endothelial cells.". Biochem. J. 360 (Pt 2): 363–70. PMID 11716764.