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acetyl-CoA acetyltransferase 1

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Target not currently curated in GtoImmuPdb

Target id: 2435

Nomenclature: acetyl-CoA acetyltransferase 1

Family: Lanosterol biosynthesis pathway

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 427 11q22.3 ACAT1 acetyl-CoA acetyltransferase 1
Mouse - 424 9 29.12 cM Acat1 acetyl-Coenzyme A acetyltransferase 1
Rat - 424 8q24 Acat1 acetyl-CoA acetyltransferase 1
Previous and Unofficial Names Click here for help
ACAT | acetoacetyl-CoA thiolase | acetyl-Co A acetyltransferase 1 mitochondrial | acetoacetyl coenzyme A thiolase
Database Links Click here for help
BRENDA
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Orphanet
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystallographic and kinetic studies of human mitochondrial acetoacetyl-CoA thiolase (T2): the importance of potassium and chloride for its structure and function
PDB Id:  2IBY
Resolution:  1.85Å
Species:  Human
References:  5
Enzyme Reaction Click here for help
EC Number: 2.3.1.9 2acetyl CoA = acetoacetyl CoA + coenzyme A
Substrates and Reaction Kinetics Click here for help
Substrate Sp. Property Value Units Standard property Standard value Assay description Assay conditions Comments Reference
acetyl CoA Substrate is endogenous in the given species Hs Km 5.08x10-4 M pKm 3.3 5
acetoacetyl CoA Substrate is endogenous in the given species Hs Km 4x10-6 M pKm 5.4 Assayed in the presence of 60µM CoA 5
coenzyme A Substrate is endogenous in the given species Hs Km 2x10-5 M pKm 4.7 Assayed in the presence of 10 µM acetoacetyl-CoA 5

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Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
compound 16 [PMID: 16242323] Small molecule or natural product Rn Inhibition 8.3 pIC50 1
pIC50 8.3 (IC50 5.4x10-9 M) [1]
compound 15b [PMID: 16242323] Small molecule or natural product Rn Inhibition 8.1 pIC50 1
pIC50 8.1 (IC50 8.3x10-9 M) [1]
SM-32504 Small molecule or natural product Rn Inhibition 8.0 pIC50 1
pIC50 8.0 (IC50 1.1x10-8 M) [1]
compound 15a [PMID: 16242323] Small molecule or natural product Rn Inhibition 7.8 pIC50 1
pIC50 7.8 (IC50 1.4x10-8 M) [1]
SMP-797 Small molecule or natural product Rn Inhibition 7.7 pIC50 1
pIC50 7.7 (IC50 2.1x10-8 M) [1]
compound 22d [PMID: 16242323] Small molecule or natural product Rn Inhibition 7.4 pIC50 1
pIC50 7.4 (IC50 4.3x10-8 M) [1]
compound 22c [PMID: 16242323] Small molecule or natural product Rn Inhibition 7.2 pIC50 1
pIC50 7.2 (IC50 6.1x10-8 M) [1]
compound 18a [PMID: 16242323] Small molecule or natural product Rn Inhibition 6.4 pIC50 1
pIC50 6.4 (IC50 3.82x10-7 M) [1]
compound 26b [PMID: 16242323] Small molecule or natural product Rn Inhibition 6.4 pIC50 1
pIC50 6.4 (IC50 4.27x10-7 M) [1]
K-604 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 6.3 pIC50 6
pIC50 6.3 (IC50 4.5x10-7 M) [6]
compound 26a [PMID: 16242323] Small molecule or natural product Rn Inhibition 6.3 pIC50 1
pIC50 6.3 (IC50 4.52x10-7 M) [1]
compound 26c [PMID: 16242323] Small molecule or natural product Rn Inhibition 6.3 pIC50 1
pIC50 6.3 (IC50 5.4x10-7 M) [1]
compound 18b [PMID: 16242323] Small molecule or natural product Rn Inhibition 6.2 pIC50 1
pIC50 6.2 (IC50 6.8x10-7 M) [1]
View species-specific inhibitor tables
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Alpha-methylacetoacetic aciduria
Synonyms: Beta-ketothiolase deficiency [Orphanet: ORPHA134] [Disease Ontology: DOID:14723]
Disease Ontology: DOID:14723
OMIM: 203750
Orphanet: ORPHA134
References:  2-4,7
Disease:  Psychomotor delay
References:  8
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human M389I G>A A rare missense mutation resulting from a G to A nucleotide change leads to a Met to Ile amino acid substitution 8

References

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1. Ban H, Muraoka M, Ioriya K, Ohashi N. (2006) Synthesis and biological activity of novel 4-phenyl-1,8-naphthyridin-2(1H)-on-3-yl ureas: potent acyl-CoA:cholesterol acyltransferase inhibitor with improved aqueous solubility. Bioorg Med Chem Lett, 16 (1): 44-8. [PMID:16242323]

2. Fukao T, Nakamura H, Song XQ, Nakamura K, Orii KE, Kohno Y, Kano M, Yamaguchi S, Hashimoto T, Orii T et al.. (1998) Characterization of N93S, I312T, and A333P missense mutations in two Japanese families with mitochondrial acetoacetyl-CoA thiolase deficiency. Hum Mutat, 12 (4): 245-54. [PMID:9744475]

3. Fukao T, Yamaguchi S, Orii T, Schutgens RB, Osumi T, Hashimoto T. (1992) 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. J Clin Invest, 89 (2): 474-9. [PMID:1346617]

4. Fukao T, Yamaguchi S, Tomatsu S, Orii T, Frauendienst-Egger G, Schrod L, Osumi T, Hashimoto T. (1991) Evidence for a structural mutation (347Ala to Thr) in a German family with 3-ketothiolase deficiency. Biochem Biophys Res Commun, 179 (1): 124-9. [PMID:1715688]

5. Haapalainen AM, Meriläinen G, Pirilä PL, Kondo N, Fukao T, Wierenga RK. (2007) Crystallographic and kinetic studies of human mitochondrial acetoacetyl-CoA thiolase: the importance of potassium and chloride ions for its structure and function. Biochemistry, 46 (14): 4305-21. [PMID:17371050]

6. Ikenoya M, Yoshinaka Y, Kobayashi H, Kawamine K, Shibuya K, Sato F, Sawanobori K, Watanabe T, Miyazaki A. (2007) A selective ACAT-1 inhibitor, K-604, suppresses fatty streak lesions in fat-fed hamsters without affecting plasma cholesterol levels. Atherosclerosis, 191 (2): 290-7. [PMID:16820149]

7. Wakazono A, Fukao T, Yamaguchi S, Hori T, Orii T, Lambert M, Mitchell GA, Lee GW, Hashimoto T. (1995) Molecular, biochemical, and clinical characterization of mitochondrial acetoacetyl-coenzyme A thiolase deficiency in two further patients. Hum Mutat, 5 (1): 34-42. [PMID:7728148]

8. Wang X, Wang H, Cao M, Li Z, Chen X, Patenia C, Gore A, Abboud EB, Al-Rajhi AA, Lewis RA et al.. (2011) Whole-exome sequencing identifies ALMS1, IQCB1, CNGA3, and MYO7A mutations in patients with Leber congenital amaurosis. Hum Mutat, 32 (12): 1450-9. [PMID:21901789]

Contributors

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