# HMG-CoA reduktaza

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| 3-hidroksi-3-metilglutaril-CoA reduktaza |
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|  PDB prikaz baziran na 1dq8. |
| Dostupne strukture |
| 1DQ8, 1DQ9, 1DQA, 1HW8, 1HW9, 1HWI, 1HWJ, 1HWK, 1HWL, 2Q1L, 2Q6B, 2Q6C, 2R4F, 3BGL, 3CCT, 3CCW, 3CCZ, 3CD0, 3CD5, 3CD7, 3CDA, 3CDB |
| Identifikatori |
| Simboli | HMGCR; LDLCQ3 |
| Vanjski ID | OMIM: 142910  MGI: 96159  HomoloGene: 30994  GeneCards: HMGCR Gene |
| EC broj | 1.1.1.34 |
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| Ontologija gena |
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| Molekularna funkcija | • aktivnost hidroksimetilglutaril-CoA reduktaze (NADPH) • aktivnost hidroksimetilglutaril-CoA reduktaze • aktivnost proteinske homodimerizacije • vezivanje koenzima • NADPH vezivanje |
| Celularna komponenta | • peroksizomalna membrana • endoplazmatični retikulum • membrana endoplazmatičnog retikuluma • integralno sa membranom |
| Biološki proces | • proces holesterolne biosinteze • starenje • respons na nutrijent • proces izoprenoidne biosinteze |

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| Pregled RNK izražavanja |
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| Ortolozi |
| Vrsta | **Čovek** | **Miš** |  |
| Entrez | 3156 | 15357 |  |
| Ensembl | ENSG00000113161 | ENSMUSG00000021670 |  |
| UniProt | P04035 | E9PVG9 |  |
| RefSeq (mRNA) | NM\_000859.2 | NM\_008255.2 |  |
| RefSeq (protein) | NP\_000850.1 | NP\_032281.2 |  |
| Lokacija (UCSC) | Chr 5: 74.63 - 74.66 Mb | Chr 13: 96.65 - 96.67 Mb |  |
| PubMed pretraga | [1] | [2] |  |

| HMG-CoA reduktaza
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| Identifikatori
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| EC broj
 | {{{EC\_number}}}
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| Ontologija gena
 | AmiGO / EGO
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| hydroxymethylglutaryl-CoA reduktaza
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| Identifikatori
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| EC broj
 | 1.1.1.88
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| CAS broj
 | 37250-24-1
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| IntEnz
 | IntEnz view
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| BRENDA
 | BRENDA entry
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| ExPASy
 | NiceZyme view
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| KEGG
 | KEGG entry
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| MetaCyc
 | metabolic pathway
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| PRIAM
 | profile
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| PDB
 | RCSB PDB PDBe PDBj PDBsum
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| Ontologija gena
 | AmiGO / EGO
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| PMC
 | articles
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| PubMed
 | articles
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| NCBI Protein
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**HMG-CoA reduktaza** (*3-hidroksi-3-metil-glutaril-CoA reduktaza*, *HMGCR*) je enzim (EC 1.1.1.88) 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.

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.

## Reference

## Literatura

* Hodge VJ, Gould SJ, Subramani S i dr.. (1992). „Normal cholesterol synthesis in human cells requires functional peroxisomes”. *Biochem. Biophys. Res. Commun.* **181** (2): 537–41. DOI:10.1016/0006-291X(91)91222-X. 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. DOI:10.1089/dna.1990.9.677. 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. PMC 552270. 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 i dr.. (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. DOI:10.1007/BF00284585. 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. DOI:10.1016/S0092-8674(85)80116-1. 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. DOI:10.1073/pnas.82.24.8567. PMC 390958. 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. DOI:10.1210/endo-117-4-1462. 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. DOI:10.1016/0020-711X(84)90120-4. 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 i dr.. (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. DOI:10.1016/0026-0495(94)90266-6. 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. DOI:10.1002/ijc.2910550421. 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 i dr.. (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. DOI:10.1177/002215549904700904. PMID 10449533.
* Honda A, Salen G, Honda M i dr.. (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. PMC 305622. 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 i dr.. (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. DOI:10.1042/0264-6021:3600363. PMC 1222236. PMID 11716764.

## Povezano

* Oksidoreduktaza

## Vanjske veze

* Cholesterol Synthesis Arhivirano 2017-07-04 na Wayback Machine-u - has some good regulatory details
* *Proteopedia HMG-CoA\_Reductase* - the HMG-CoA Reductase Structure in Interactive 3D