HMG-CoA reduktaza (3-hidroksi-3-metil-glutaril-CoA reduktaza, HMGCR) je enzim (EC1.1.1.88) koji ograničava brzinu mevalonatnog puta, metaboličkog puta koji proizvodi holesterol i druge izoprenoide. Normalno je u ćelijama sisara ovaj enzim supresovan holesterolom koji potiče iz internalizacije i degradacije lipoproteina niske gustine (LDL) putem LDL receptora, kao i oksidovanim vrstama holesterola. Kompetitivni inhibitori reduktaze indukuju izražavanje LDL receptora u jeri, čime se povećava katabolizam LDL-a u plazmi, te se snižava koncentracija holesterola u plazmi, što je važna odrednica ateroskleroze.[1]
Ovaj enzim je biološka meta široko dostupnih lekova za snižavanje nivoa holesterola, kolektivno poznatih kao statini. HMG-CoA reduktaza ze vezana za membranu endoplazmatičnog retikuluma, i dugo se mislilo da ima sedam transmembranskih domena, sa aktivnim mestom lociranim na njenom dugačkom karboksilnom domenu u citozolu. Nedavni nalazi su pokazali da sadrži osam transmembranskih domena.[2]
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. PMID1755834. doi:10.1016/0006-291X(91)91222-X.
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. PMID1979742. doi:10.1089/dna.1990.9.677.
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. PMID2991281.
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. PMID2998972. doi:10.1007/BF00284585.
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. PMID3308873.
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. PMID3860301. doi:10.1016/S0092-8674(85)80116-1.
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. PMID3896758. doi:10.1210/endo-117-4-1462.
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. PMID6479432. doi:10.1016/0020-711X(84)90120-4.
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. PMID8406993. doi:10.1002/ijc.2910550421.
Van Doren M, Broihier HT, Moore LA, Lehmann R (1998). „HMG-CoA reductase guides migrating primordial germ cells”. Nature. 396 (6710): 466—9. PMID9853754. doi:10.1038/24871.
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. PMID10391209. doi:10.1038/10290.
Aboushadi N, Engfelt WH, Paton VG, Krisans SK (1999). „Role of peroxisomes in isoprenoid biosynthesis”. J. Histochem. Cytochem. 47 (9): 1127—32. PMID10449533. doi:10.1177/002215549904700904.
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. PMID10695663. doi:10.1067/mlc.2000.104459.
. PMID 1374417. doi:10.1083/jcb.117.5.959.
