Butyrate—CoA ligase

Butyrate—CoA ligase (also known as butyryl-CoA synthetase) is an enzyme that catalyzes the conversion of butyrate (butanoate) and coenzyme A (CoA) into butyryl-CoA and adenosine monophosphate (AMP) in the presence of ATP. This reaction is part of the fatty acid metabolism pathway, playing a crucial role in the breakdown and utilization of fatty acids for energy production. Butyrate—CoA ligase is encoded by the ACSM2A gene in humans.

Function

Butyrate—CoA ligase is involved in the metabolism of short-chain fatty acids (SCFAs), which are important sources of energy for the colonocytes in the human colon. SCFAs, including butyrate, are produced by the bacterial fermentation of dietary fibers in the gut. The enzyme facilitates the activation of butyrate, enabling its entry into the mitochondria where it undergoes beta-oxidation to produce acetyl-CoA, which is then utilized in the citric acid cycle (TCA cycle) for energy production.

Structure

The enzyme belongs to the family of ligases, specifically those forming carbon-sulfur bonds as acid-thiol ligases. The structure of butyrate—CoA ligase has been elucidated through X-ray crystallography, revealing a large domain for ATP binding and a smaller domain for substrate binding. This structure is crucial for the enzyme's function, as it undergoes conformational changes during the catalytic cycle to facilitate substrate binding and product release.

Clinical Significance

Butyrate—CoA ligase plays a significant role in the metabolic processes of the gut microbiota and the host's energy metabolism. Alterations in the production or activity of this enzyme can affect the concentration of butyrate in the gut, which has been linked to various health conditions, including inflammatory bowel disease (IBD), colon cancer, and metabolic syndrome. Butyrate has anti-inflammatory properties and serves as a primary energy source for colonocytes, highlighting the importance of butyrate—CoA ligase in maintaining gut health and preventing disease.

Genetic Regulation

The expression of the ACSM2A gene, which encodes butyrate—CoA ligase, is regulated by various factors, including dietary components and the gut microbiota composition. Research is ongoing to understand the complex regulatory mechanisms that control the activity of this enzyme and its impact on human health.

See Also

• Fatty acid metabolism
• Coenzyme A
• Short-chain fatty acid
• Gut microbiota