Acetyl-CoA C-acyltransferase

Acetyl-CoA C-acyltransferase (ACACT) is an enzyme that plays a crucial role in metabolism, specifically in the fatty acid metabolism pathway. This enzyme is involved in the beta-oxidation process, where it catalyzes the third step, facilitating the conversion of acyl-CoA and acetyl-CoA from fatty acids for energy production. The activity of acetyl-CoA C-acyltransferase is essential for the breakdown of fatty acids into acetyl-CoA, which can then enter the citric acid cycle (TCA cycle) to produce energy.

Function

Acetyl-CoA C-acyltransferase functions within the mitochondria and peroxisomes of cells. In the beta-oxidation pathway, it catalyzes the thiolysis of 3-ketoacyl-CoA to form acetyl-CoA and a shortened acyl-CoA molecule. This reaction is critical for the stepwise degradation of fatty acids, allowing for the efficient production of energy in the form of ATP. The enzyme's activity is particularly important during periods of fasting or low-carbohydrate diets when the body relies more heavily on fat as an energy source.

Structure

The enzyme is encoded by the gene ACAA2 in humans. It is a multimeric protein, typically existing as a homotetramer. The structure of acetyl-CoA C-acyltransferase includes a catalytic triad that is essential for its enzymatic activity. This triad consists of Cysteine, Histidine, and Aspartate amino acid residues, which play a critical role in the mechanism of the enzyme.

Clinical Significance

Mutations in the ACAA2 gene can lead to deficiencies in acetyl-CoA C-acyltransferase activity. Such deficiencies can result in metabolic disorders, including ketone body metabolism disturbances and fatty acid oxidation disorders. Patients with these conditions may exhibit symptoms such as hypoglycemia, muscle weakness, and cardiomyopathy. Early diagnosis and management are crucial for preventing severe metabolic crises.

See Also

• Fatty acid metabolism
• Beta-oxidation
• Citric acid cycle
• Metabolic disorder