acetyl-CoA acetyltransferase 1 | Lanosterol biosynthesis pathway | IUPHAR/MMV Guide to MALARIA PHARMACOLOGY

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acetyl-CoA acetyltransferase 1

Target id: 2435

Nomenclature: acetyl-CoA acetyltransferase 1

Family: Lanosterol biosynthesis pathway

Annotation status:  image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 427 11q22.3 ACAT1 acetyl-CoA acetyltransferase 1
Mouse - 424 9 C-D Acat1 acetyl-Coenzyme A acetyltransferase 1
Rat - 424 8q24.1 Acat1 acetyl-CoA acetyltransferase 1
Previous and Unofficial Names
ACAT | acetoacetyl-CoA thiolase | acetyl-Co A acetyltransferase 1 mitochondrial | acetoacetyl coenzyme A thiolase
Database Links
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
RefSeq Nucleotide
RefSeq Protein
Selected 3D Structures
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
Resolution:  1.85Å
Species:  Human
References:  5
Enzyme Reaction
EC Number: 2acetyl CoA = acetoacetyl CoA + coenzyme A
Substrates and Reaction Kinetics
Substrate Sp. Property Value Units Standard property Standard value Assay description Assay conditions Comments Reference
acetyl CoA Hs Km 5.08x10-4 M pKm 3.3 5
acetoacetyl CoA Hs Km 4x10-6 M pKm 5.4 Assayed in the presence of 60µM CoA 5
coenzyme A Hs Km 2x10-5 M pKm 4.7 Assayed in the presence of 10 µM acetoacetyl-CoA 5

Download all structure-activity data for this target as a CSV file

Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
compound 16 [PMID: 16242323] Rn Inhibition 8.3 pIC50 1
pIC50 8.3 (IC50 5.4x10-9 M) [1]
compound 15b [PMID: 16242323] Rn Inhibition 8.1 pIC50 1
pIC50 8.1 (IC50 8.3x10-9 M) [1]
SM-32504 Rn Inhibition 8.0 pIC50 1
pIC50 8.0 (IC50 1.1x10-8 M) [1]
compound 15a [PMID: 16242323] Rn Inhibition 7.8 pIC50 1
pIC50 7.8 (IC50 1.4x10-8 M) [1]
SMP-797 Rn Inhibition 7.7 pIC50 1
pIC50 7.7 (IC50 2.1x10-8 M) [1]
compound 22d [PMID: 16242323] Rn Inhibition 7.4 pIC50 1
pIC50 7.4 (IC50 4.3x10-8 M) [1]
compound 22c [PMID: 16242323] Rn Inhibition 7.2 pIC50 1
pIC50 7.2 (IC50 6.1x10-8 M) [1]
compound 18a [PMID: 16242323] Rn Inhibition 6.4 pIC50 1
pIC50 6.4 (IC50 3.82x10-7 M) [1]
compound 26b [PMID: 16242323] Rn Inhibition 6.4 pIC50 1
pIC50 6.4 (IC50 4.27x10-7 M) [1]
K-604 Hs Inhibition 6.3 pIC50 6
pIC50 6.3 (IC50 4.5x10-7 M) [6]
compound 26a [PMID: 16242323] Rn Inhibition 6.3 pIC50 1
pIC50 6.3 (IC50 4.52x10-7 M) [1]
compound 26c [PMID: 16242323] Rn Inhibition 6.3 pIC50 1
pIC50 6.3 (IC50 5.4x10-7 M) [1]
compound 18b [PMID: 16242323] 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
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


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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]


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