ACAT1

The ACAT1 gene provides instructions for making an enzyme that is found in the energy-producing centers within cells (mitochondria). This enzyme plays an essential role in breaking down proteins and fats from the diet. Specifically, it helps process isoleucine, an amino acid that is a building block of many proteins. This enzyme is also involved in processing ketones, which are molecules that are produced when fats are broken down in the body.

During the breakdown of proteins, the ACAT1 enzyme is responsible for the last step in processing isoleucine. It converts a molecule called 2-methyl-acetoacetyl-coenzyme A (CoA) into two smaller molecules, propionyl-CoA and acetyl-CoA, that can be used to produce energy.

The ACAT1 enzyme carries out the last step in ketone breakdown (ketolysis) during the processing of fats. The enzyme converts a molecule called acetoacetyl-CoA into two molecules of acetyl-CoA, which can be used to produce energy. In the liver, the enzyme also carries out this chemical reaction in reverse, which is the first step in building new ketones (ketogenesis).

beta-ketothiolase deficiency - caused by mutations in the ACAT1 gene

More than 40 mutations in the ACAT1 gene have been identified in people with beta-ketothiolase deficiency. Some of these genetic changes disrupt the normal function of the enzyme, while other mutations prevent cells from producing any functional enzyme.

A shortage of the ACAT1 enzyme prevents the body from processing proteins and fats properly. As a result, chemical byproducts called organic acids can build up to toxic levels in the blood. These substances cause the blood to become too acidic (ketoacidosis), which can damage the body's tissues and organs, particularly in the nervous system. This damage leads to episodes of vomiting, dehydration, and other health problems associated with beta-ketothiolase deficiency.