AACS - Acetoacetyl-CoA Synthetase |Elisa - Clia - Antibody - Protein

Background:

The acetoacetyl-CoA synthetase (AACS) gene encodes a protein of the same name, which converts acetoacetate to acetoacetyl-CoA, and plays a crucial role in ketone body utilization and fatty acid synthesis. The gene is found on human chromosome 12. Ketone bodies, unlike fatty acids and triglycerides, are water-soluble. They are exported from the liver, and are taken up by other tissues, notably brain and skeletal and cardiac muscle. There, they are broken down to acetyl-CoA which is oxidized via the TCA cycle to yield energy. In a normal person, this pathway of ketone body synthesis and utilization is most active during extended periods of fasting. Under these conditions, mobilization and breakdown of stored fatty acids generates abundant acetyl-CoA acetyl-CoA in liver cells for synthesis of ketone bodies, and their utilization in other tissues minimizes the demand of these tissues for glucose

Function:

AACS catalyzes the conversion of acetoacetate and CoA to acetoacetyl-CoA in the presence of ATP. This reaction is a crucial step in the synthesis of ketone bodies, which are important energy sources, particularly during fasting or periods of prolonged exercise when glucose availability is limited.

Main Features:

1. Substrate Specificity: AACS specifically catalyzes the activation of acetoacetate, a ketone body, to form acetoacetyl-CoA, a key intermediate in lipid metabolism.
2. ATP-dependent Reaction: The enzymatic activity of AACS requires ATP as a cofactor to drive the formation of acetoacetyl-CoA.
3. Regulation: The activity of AACS is regulated by various factors, including substrate availability, hormonal signals, and cellular energy status.

Biological Significance:

1. Ketogenesis: AACS is involved in the synthesis of ketone bodies, such as acetoacetate and β-hydroxybutyrate, which serve as alternative energy sources during periods of fasting, starvation, or prolonged exercise when glucose availability is limited.
2. Lipid Metabolism: Acetoacetyl-CoA, the product of the AACS-catalyzed reaction, is an important intermediate in fatty acid metabolism, serving as a precursor for the synthesis of cholesterol, steroids, and other lipids.
3. Energy Homeostasis: Ketone bodies produced by AACS-mediated ketogenesis provide an alternative fuel source for tissues such as the brain, heart, and skeletal muscles when glucose levels are low, helping to maintain energy homeostasis.

Clinical Issues:

1. Ketogenesis Disorders: Dysregulation of AACS activity or mutations in the AACS gene can lead to abnormalities in ketone body synthesis, resulting in metabolic disorders such as ketoacidosis, a potentially life-threatening condition characterized by elevated levels of ketone bodies in the blood.
2. Lipid Metabolism Disorders: Alterations in AACS function may disrupt lipid metabolism, contributing to metabolic disorders such as dyslipidemia, obesity, and fatty liver disease.
3. Neurological Disorders: Ketone bodies produced by AACS-mediated ketogenesis play a critical role in providing energy to the brain during periods of glucose deprivation. Dysregulation of ketone body metabolism may impact neurological function and contribute to neurological disorders such as epilepsy and neurodegenerative diseases.