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Gene Review

ACAT1  -  acetyl-CoA acetyltransferase 1

Homo sapiens

Synonyms: ACAT, Acetoacetyl-CoA thiolase, Acetyl-CoA acetyltransferase, mitochondrial, MAT, T2, ...
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Disease relevance of ACAT1


High impact information on ACAT1

  • GK07 is a compound heterozygote; the maternal allele has a novel G to T transversion at position 1136 causing Gly379 to Val substitution (G379V) of the T2 precursor [2].
  • 3-Ketothiolase deficiency (3KTD) stems from a deficiency of mitochondrial acetoacetyl-coenzyme A thiolase (T2) [3].

Biological context of ACAT1

  • There are two adjacent in-frame AUG codons, AUG(1397-1399) and AUG(1415-1417), at 5'-terminus of the open reading frame (ORF, nt 1397-3049) of human ACAT1 mRNA corresponding to cDNA K1 [4].
  • Much has been learned from mice with gene deletions for either ACAT1 or ACAT2 [5].
  • Mass-production of human ACAT-1 and ACAT-2 to screen isoform-specific inhibitor: a different substrate specificity and inhibitory regulation [6].
  • To develop more potent hACAT inhibitor, shikonin derivatives (5-11) were synthesized by semi-synthesis of shikonin (4), which was prepared by hydrolysis of 1-3 [7].

Anatomical context of ACAT1

  • Studies in non-human primates have shown the presence of ACAT1 primarily in the Kupffer cells of the liver, in non-mucosal cell types in the intestine, and in kidney and adrenal cortical cells, whereas ACAT2 is present only in hepatocytes and in intestinal mucosal cells [8].
  • We conclude that under various pathologic conditions, fully differentiated macrophages express ACAT2 in addition to ACAT1 [9].
  • ACAT1 is ubiquitously expressed, whereas ACAT2 is primarily expressed in intestinal mucosa and plays an important role in intestinal cholesterol absorption [10].

Associations of ACAT1 with chemical compounds

  • Pactimibe exhibited dual inhibition for ACAT1 and ACAT2 (concentrations inhibiting 50% [IC50s] at micromolar levels) more potently than avasimibe [11].
  • These results suggest that ACAT1/2 dual inhibitor pactimibe has anti-atherosclerotic potential beyond its plasma cholesterol-lowering activity [11].
  • Known ACAT inhibitors, pyripyropene A, oleic acid anilide, and diethyl pyrocarbonate, were tested to evaluate the inhibitory specificity and sensitivity of the expressed enzymes [6].
  • Furthermore, cholesterol was more rapidly utilized by hACAT-1, but hACAT-2 esterified other cholic acid derivatives more efficiently [6].
  • Human ACAT inhibitory effects of shikonin derivatives from Lithospermum erythrorhizon [7].

Other interactions of ACAT1


Analytical, diagnostic and therapeutic context of ACAT1

  • Furthermore, RT-PCR clearly revealed the presence of both ACAT1 and ACAT2 mRNAs in human atherosclerotic aorta [9].
  • The expressed hACAT-1 and hACAT-2 appeared as a 50 kDa- and a 46 kDa-band on SDS-PAGE, respectively, from Hi5 cells and they preferred to exist in oligomeric form, from dimer to tetramer, during the purification process [6].
  • Sequence analysis of an isolated, full-length clone of ACAT2 cDNA identified an open reading frame encoding a 526-amino acid protein with essentially no sequence similarity to the ACAT1 cDNA over the N-terminal 101 amino acids but with 57% identity predicted over the remaining 425 amino acids [17].
  • The expression of ACAT1 and ACAT2 was measured by TaqMan real-time quantitative PCR normalized to 18s ribosomal RNA [18].
  • Western blot analysis also showed a higher level of ACAT1 protein in the duodenum of high responders than in that of low responders [18].





  1. A patient with severe neurologic symptoms and acetoacetyl-CoA thiolase deficiency. Groot, C.J., Haan, G.L., Hulstaert, C.E., Hoomes, F.A. Pediatr. Res. (1977) [Pubmed]
  2. Identification of a novel exonic mutation at -13 from 5' splice site causing exon skipping in a girl with mitochondrial acetoacetyl-coenzyme A thiolase deficiency. Fukao, T., Yamaguchi, S., Wakazono, A., Orii, T., Hoganson, G., Hashimoto, T. J. Clin. Invest. (1994) [Pubmed]
  3. Identification of three mutant alleles of the gene for mitochondrial acetoacetyl-coenzyme A thiolase. A complete analysis of two generations of a family with 3-ketothiolase deficiency. Fukao, T., Yamaguchi, S., Orii, T., Schutgens, R.B., Osumi, T., Hashimoto, T. J. Clin. Invest. (1992) [Pubmed]
  4. A stable upstream stem-loop structure enhances selection of the first 5'-ORF-AUG as a main start codon for translation initiation of human ACAT1 mRNA. Yang, L., Chen, J., Chang, C.C., Yang, X.Y., Wang, Z.Z., Chang, T.Y., Li, B.L. Acta Biochim. Biophys. Sin. (Shanghai) (2004) [Pubmed]
  5. ACAT2 is a target for treatment of coronary heart disease associated with hypercholesterolemia. Rudel, L.L., Lee, R.G., Parini, P. Arterioscler. Thromb. Vasc. Biol. (2005) [Pubmed]
  6. Mass-production of human ACAT-1 and ACAT-2 to screen isoform-specific inhibitor: a different substrate specificity and inhibitory regulation. Cho, K.H., An, S., Lee, W.S., Paik, Y.K., Kim, Y.K., Jeong, T.S. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  7. Human ACAT inhibitory effects of shikonin derivatives from Lithospermum erythrorhizon. An, S., Park, Y.D., Paik, Y.K., Jeong, T.S., Lee, W.S. Bioorg. Med. Chem. Lett. (2007) [Pubmed]
  8. Acyl coenzyme A: cholesterol acyltransferase types 1 and 2: structure and function in atherosclerosis. Rudel, L.L., Lee, R.G., Cockman, T.L. Curr. Opin. Lipidol. (2001) [Pubmed]
  9. Acyl-coenzyme A:cholesterol acyltransferase 2 (ACAT2) is induced in monocyte-derived macrophages: in vivo and in vitro studies. Sakashita, N., Miyazaki, A., Chang, C.C., Chang, T.Y., Kiyota, E., Satoh, M., Komohara, Y., Morganelli, P.M., Horiuchi, S., Takeya, M. Lab. Invest. (2003) [Pubmed]
  10. Human acyl-CoA:cholesterol acyltransferase 2 gene expression in intestinal Caco-2 cells and in hepatocellular carcinoma. Song, B.L., Wang, C.H., Yao, X.M., Yang, L., Zhang, W.J., Wang, Z.Z., Zhao, X.N., Yang, J.B., Qi, W., Yang, X.Y., Inoue, K., Lin, Z.X., Zhang, H.Z., Kodama, T., Chang, C.C., Liu, Y.K., Chang, T.Y., Li, B.L. Biochem. J. (2006) [Pubmed]
  11. Importance of acyl-coenzyme A:cholesterol acyltransferase 1/2 dual inhibition for anti-atherosclerotic potency of pactimibe. Kitayama, K., Tanimoto, T., Koga, T., Terasaka, N., Fujioka, T., Inaba, T. Eur. J. Pharmacol. (2006) [Pubmed]
  12. Enzymes of ketone body utilization in human tissues: protein and messenger RNA levels of succinyl-coenzyme A (CoA):3-ketoacid CoA transferase and mitochondrial and cytosolic acetoacetyl-CoA thiolases. Fukao, T., Song, X.Q., Mitchell, G.A., Yamaguchi, S., Sukegawa, K., Orii, T., Kondo, N. Pediatr. Res. (1997) [Pubmed]
  13. Towards compendia of negative genetic association studies: an example for Alzheimer disease. Blomqvist, M.E., Reynolds, C., Katzov, H., Feuk, L., Andreasen, N., Bogdanovic, N., Blennow, K., Brookes, A.J., Prince, J.A. Hum. Genet. (2006) [Pubmed]
  14. Role of the N-terminal hydrophilic domain of acyl-coenzyme A:cholesterol acyltransferase 1 on the enzyme's quaternary structure and catalytic efficiency. Yu, C., Zhang, Y., Lu, X., Chen, J., Chang, C.C., Chang, T.Y. Biochemistry (2002) [Pubmed]
  15. Activities of 3-hydroxybutyrate dehydrogenase, 3-oxoacid CoA-transferase and acetoacetyl-CoA thiolase in relation to ketone-body utilisation in muscles from vertebrates and invertebrates. Beis, A., Zammit, V.A., Newsholme, E.A. Eur. J. Biochem. (1980) [Pubmed]
  16. Inborn errors of isoleucine degradation: A review. Korman, S.H. Mol. Genet. Metab. (2006) [Pubmed]
  17. Identification of a form of acyl-CoA:cholesterol acyltransferase specific to liver and intestine in nonhuman primates. Anderson, R.A., Joyce, C., Davis, M., Reagan, J.W., Clark, M., Shelness, G.S., Rudel, L.L. J. Biol. Chem. (1998) [Pubmed]
  18. Expression levels of ACAT1 and ACAT2 genes in the liver and intestine of baboons with high and low lipemic responses to dietary lipids. Kushwaha, R.S., Rosillo, A., Rodriguez, R., McGill, H.C. J. Nutr. Biochem. (2005) [Pubmed]
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