ACAT2
Acetyl-CoA acetyltransferase, cytosolic, also known as cytosolic acetoacetyl-CoA thiolase, is an enzyme that in humans is encoded by the ACAT2 (acetyl-Coenzyme A acetyltransferase 2) gene[1][2] that is responsible for the synthesis of cholesteryl esters which are part of lipoproteins containing apoB.
Acetyl-Coenzyme A acetyltransferase 2 is an acetyl-CoA C-acetyltransferase enzyme.
Gene
This gene shows complementary overlapping with the 3-prime region of the TCP1 gene in both mouse and human. These genes are encoded on opposite strands of DNA, as well as in opposite transcriptional orientation.[1]
Function
The product of this gene is an enzyme involved in lipid metabolism, and it encodes cytosolic acetoacetyl-CoA thiolase.[1]
In a study done on rats, it was found that rats fed a fat-enriched diet whose ACAT2 gene were deleted were protected from dietary fat-induced atherosclerosis. LDL concentration, CE composition, and particle size were affected in ways that reduced atherogenesis in comparison to other rats whose ACAT2 gene were not modified.[3]
References
Further reading
- Locke JA, Wasan KM, Nelson CC, et al. (2008). "Androgen-mediated cholesterol metabolism in LNCaP and PC-3 cell lines is regulated through two different isoforms of acyl-coenzyme A:Cholesterol Acyltransferase (ACAT).". Prostate 68 (1): 20–33. doi:10.1002/pros.20674. PMID 18000807.
- Reynolds CA, Hong MG, Eriksson UK, et al. (2010). "Analysis of lipid pathway genes indicates association of sequence variation near SREBF1/TOM1L2/ATPAF2 with dementia risk.". Hum. Mol. Genet. 19 (10): 2068–78. doi:10.1093/hmg/ddq079. PMID 20167577.
- He X, Lu Y, Saha N, et al. (2005). "Acyl-CoA: cholesterol acyltransferase-2 gene polymorphisms and their association with plasma lipids and coronary artery disease risks.". Hum. Genet. 118 (3-4): 393–403. doi:10.1007/s00439-005-0055-3. PMID 16195894.
- Yamada Y, Matsuo H, Warita S, et al. (2007). "Prediction of genetic risk for dyslipidemia.". Genomics 90 (5): 551–8. doi:10.1016/j.ygeno.2007.08.001. PMID 17919884.
- Kursula P, Sikkilä H, Fukao T, et al. (2005). "High resolution crystal structures of human cytosolic thiolase (CT): a comparison of the active sites of human CT, bacterial thiolase, and bacterial KAS I.". J. Mol. Biol. 347 (1): 189–201. doi:10.1016/j.jmb.2005.01.018. PMID 15733928.
- Lu Y, Dollé ME, Imholz S, et al. (2008). "Multiple genetic variants along candidate pathways influence plasma high-density lipoprotein cholesterol concentrations.". J. Lipid Res. 49 (12): 2582–9. doi:10.1194/jlr.M800232-JLR200. PMID 18660489.
- Mungall AJ, Palmer SA, Sims SK, et al. (2003). "The DNA sequence and analysis of human chromosome 6.". Nature 425 (6960): 805–11. doi:10.1038/nature02055. PMID 14574404.
- Parini P, Jiang ZY, Einarsson C, et al. (2009). "ACAT2 and human hepatic cholesterol metabolism: identification of important gender-related differences in normolipidemic, non-obese Chinese patients.". Atherosclerosis 207 (1): 266–71. doi:10.1016/j.atherosclerosis.2009.04.010. PMID 19467657.
- Pramfalk C, Angelin B, Eriksson M, Parini P (2007). "Cholesterol regulates ACAT2 gene expression and enzyme activity in human hepatoma cells.". Biochem. Biophys. Res. Commun. 364 (2): 402–9. doi:10.1016/j.bbrc.2007.10.028. PMID 17950700.
- Suzuki Y, Yamashita R, Shirota M, et al. (2004). "Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions.". Genome Res. 14 (9): 1711–8. doi:10.1101/gr.2435604. PMC 515316. PMID 15342556. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=515316.
- Yoshida T, Kato K, Yokoi K, et al. (2009). "Association of candidate gene polymorphisms with chronic kidney disease in Japanese individuals with hypertension.". Hypertens. Res. 32 (5): 411–8. doi:10.1038/hr.2009.22. PMID 19282863.
- Matsumoto K, Fujiwara Y, Nagai R, et al. (2008). "Expression of two isozymes of acyl-coenzyme A: cholesterol acyltransferase-1 and -2 in clear cell type renal cell carcinoma.". Int. J. Urol. 15 (2): 166–70. doi:10.1111/j.1442-2042.2007.01947.x. PMID 18269457.
- Yao XM, Wang CH, Song BL, et al. (2005). "Two human ACAT2 mRNA variants produced by alternative splicing and coding for novel isoenzymes.". Acta Biochim. Biophys. Sin. (Shanghai) 37 (12): 797–806. PMID 16331323.
- Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=528928.
- Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs.". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
- Ohta T, Takata K, Katsuren K, Fukuyama S (2004). "The influence of the acyl-CoA:cholesterol acyltransferase-1 gene (-77G-->A) polymorphisms on plasma lipid and apolipoprotein levels in normolipidemic and hyperlipidemic subjects.". Biochim. Biophys. Acta 1682 (1-3): 56–62. doi:10.1016/j.bbalip.2004.01.008. PMID 15158756.
- Ruaño G, Bernene J, Windemuth A, et al. (2009). "Physiogenomic comparison of edema and BMI in patients receiving rosiglitazone or pioglitazone.". Clin. Chim. Acta 400 (1-2): 48–55. doi:10.1016/j.cca.2008.10.009. PMID 18996102.
- Jiang ZY, Jiang CY, Wang L, et al. (2009). "Increased NPC1L1 and ACAT2 expression in the jejunal mucosa from Chinese gallstone patients.". Biochem. Biophys. Res. Commun. 379 (1): 49–54. doi:10.1016/j.bbrc.2008.11.131. PMID 19071091.
- Ewing RM, Chu P, Elisma F, et al. (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry.". Mol. Syst. Biol. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1847948.
PDB gallery
|
|
|
1wl4: Human cytosolic acetoacetyl-CoA thiolase complexed with CoA
|
|
1wl5: Human cytosolic acetoacetyl-CoA thiolase
|
|
|
|
This article incorporates text from the United States National Library of Medicine, which is in the public domain.