HMG-CoA reduktaza
edit |
3-hidroksi-3-metilglutaril-CoA reduktaza | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
![]() 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 | ||||||||||
| |||||||||||
Pregled RNK izražavanja | |||||||||||
![]() | |||||||||||
![]() | |||||||||||
podaci | |||||||||||
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 | |||
---|---|---|---|
Identifikatori | |||
EC broj | {{{EC_number}}} | ||
Ontologija gena | AmiGO / EGO | ||
|
hydroxymethylglutaryl-CoA reduktaza | |||||||||
---|---|---|---|---|---|---|---|---|---|
Identifikatori | |||||||||
EC broj | 1.1.1.88 | ||||||||
CAS broj | 37250-24-1 | ||||||||
IntEnz | IntEnz view | ||||||||
BRENDA | BRENDA entry | ||||||||
ExPASy | NiceZyme view | ||||||||
KEGG | KEGG entry | ||||||||
MetaCyc | metabolic pathway | ||||||||
PRIAM | profile | ||||||||
PDB | RCSB PDB PDBe PDBj PDBsum | ||||||||
Ontologija gena | AmiGO / EGO | ||||||||
|
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.[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]
Reference
- ↑ „Entrez Gene: HMGCR 3-hydroxy-3-methylglutaryl-Coenzyme A reductase”.
- ↑ Roitelman J, Olender EH, Bar-Nun S, Dunn WA, Simoni RD (June 1992). „Immunological evidence for eight spans in the membrane domain of 3-hydroxy-3-methylglutaryl coenzyme A reductase: implications for enzyme degradation in the endoplasmic reticulum”. J. Cell Biol. 117 (5): 959–73. DOI:10.1083/jcb.117.5.959. PMC 2289486. PMID 1374417.
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
Spoljašnje 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
- p
- r
- u
|