ACAT1

This gene encodes a mitochondrially localized enzyme that catalyzes the reversible formation of acetoacetyl-CoA from two molecules of acetyl-CoA. Defects in this gene are associated with 3-ketothiolase deficiency, an inborn error of isoleucine catabolism characterized by urinary excretion of 2-methyl-3-hydroxybutyric acid, 2-methylacetoacetic acid, tiglylglycine, and butanone. [provided by RefSeq, Feb 2009]

Full Name

Acetyl-CoA Acetyltransferase 1

Function

This is one of the enzymes that catalyzes the last step of the mitochondrial beta-oxidation pathway, an aerobic process breaking down fatty acids into acetyl-CoA. Using free coenzyme A/CoA, catalyzes the thiolytic cleavage of medium- to long-chain 3-oxoacyl-CoAs into acetyl-CoA and a fatty acyl-CoA shortened by two carbon atoms. The activity of the enzyme is reversible and it can also catalyze the condensation of two acetyl-CoA molecules into acetoacetyl-CoA. Thereby, it plays a major role in ketone body metabolism.

Biological Process

Acetyl-CoA biosynthetic process
Acetyl-CoA catabolic process
Branched-chain amino acid catabolic process
Cholesterol esterification
Coenzyme A biosynthetic process
Coenzyme A metabolic process
Fatty acid beta-oxidation
Isoleucine catabolic process
Ketone body biosynthetic process
Ketone body catabolic process
Ketone body metabolic process
Propionyl-CoA biosynthetic process

Cellular Location

Mitochondrion

Involvement in disease

An autosomal recessive inborn error of isoleucine catabolism characterized by intermittent ketoacidotic attacks associated with unconsciousness. Some patients die during an attack or are mentally retarded. Urinary excretion of 2-methyl-3-hydroxybutyric acid, 2-methylacetoacetic acid, triglylglycine, butanone is increased. It seems likely that the severity of this disease correlates better with the environmental or acquired factors than with the ACAT1 genotype.

PTM

Succinylation at Lys-268, adjacent to a coenzyme A binding site. Desuccinylated by SIRT5 (By similarity).