ACAT1 mutants don't synthesize propionyl-CoA or acetyl-CoA

Stable Identifier
R-HSA-9915356
Type
Reaction [transition]
Species
Homo sapiens
Compartment
mitochondrial matrix
ReviewStatus
5/5
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ACAT1 mutants don't synthesize propionyl-CoA or acetyl-CoA
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Mutations in ACAT1 have been identified in cases of beta-ketothiolase deficiency, an inborn error of metabolism related to the isoleucine breakdown pathway and ketone body metabolism (reviewed in Korman et al, 2006; Fukao et al, 2019). Although there is no clear relationship between clinical manifestations of the disorder and the genotype, the following mutations have been identified in patients showing a range of clinical symptoms, have been demonstrated to have severely to completely reduced enzymatic activity in vitro and are annotated as "pathogenic" or "likely pathogenic" by ClinVar.
N93S: Fukao et al, 1998
N158D: Wakazono et al, 1995
G183R: Fukao et al, 1992
A301P: Wakazono et al, 1995
A333P: Fukao et al, 1998
Literature References
PubMed ID Title Journal Year
1346617 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

Osumi, T, Hashimoto, T, Orii, T, Yamaguchi, S, Fukao, T, Schutgens, RB

J Clin Invest 1992
16950638 Inborn errors of isoleucine degradation: a review

Korman, SH

Mol Genet Metab 2006
9744475 Characterization of N93S, I312T, and A333P missense mutations in two Japanese families with mitochondrial acetoacetyl-CoA thiolase deficiency

Nakamura, K, Orii, KE, Hashimoto, T, Kano, M, Orii, T, Nakamura, H, Kondo, N, Yamaguchi, S, Fukao, T, Kohno, Y, Song, XQ

Hum Mutat 1998
30393371 Recent advances in understanding beta-ketothiolase (mitochondrial acetoacetyl-CoA thiolase, T2) deficiency

Otsuka, H, Sasai, H, Ago, Y, Matsumoto, H, Fukao, T, Abdelkreem, E, Aoyama, Y

J Hum Genet 2019
7728148 Molecular, biochemical, and clinical characterization of mitochondrial acetoacetyl-coenzyme A thiolase deficiency in two further patients

Wakazono, A, Lambert, M, Hashimoto, T, Mitchell, GA, Orii, T, Yamaguchi, S, Fukao, T, Lee, GW, Hori, T

Hum Mutat 1995
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Catalyst Activity

acetyl-CoA C-acetyltransferase activity of ACAT1 mutant tetramer [mitochondrial matrix]

Physical Entity
ACAT1 mutant tetramer [mitochondrial matrix] (Homo sapiens)
Activity
acetyl-CoA C-acetyltransferase activity (GO:0003985)
Normal reaction
alpha-methylacetoacetyl-CoA + CoA => propionyl-CoA + acetyl-CoA (Homo sapiens)
Functional status

Loss of function of ACAT1 mutant tetramer [mitochondrial matrix]

Normal Entity
Disease Entity
Status
Disease
Name Identifier Synonyms
beta-ketothiolase deficiency DOID:14723 3-ketothiolase deficiency, 3-oxothiolase deficiency, Mitochondrial acetoacetyl-CoA Thiolase deficiency, 2-methyl-3-hydroxybutyricacidemia, alpha-methylacetoaceticaciduria, peroxisomal thiolase deficiency
Authored
Rothfels, K  (2024-07-29)
Reviewed
D'Eustachio, P  (2024-08-18)
Created
Rothfels, K  (2024-07-04)
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