Biotin—CoA ligase

Biotin—CoA ligase is an enzyme that plays a crucial role in fatty acid metabolism and biotin or vitamin B7 utilization. This enzyme catalyzes the formation of biotinyl-CoA from biotin and CoA, a key step in the biotin cycle that is essential for the synthesis and breakdown of fatty acids and for the regulation of gene expression.

Function

Biotin—CoA ligase is involved in the carboxylation and decarboxylation processes that are central to the metabolism of carbohydrates, fats, and proteins. It activates biotin to biotinyl-CoA, which is then used to carboxylate specific enzyme substrates, playing a pivotal role in gluconeogenesis, fatty acid synthesis, and the catabolism of certain amino acids. Through these processes, it contributes to maintaining the body's energy balance and the synthesis of important metabolic intermediates.

Structure

The structure of Biotin—CoA ligase is characterized by a large domain that binds ATP and a smaller domain that binds biotin and CoA. The active site of the enzyme is located at the interface of these two domains. The enzyme undergoes a significant conformational change upon binding of its substrates, which is crucial for its catalytic activity.

Mechanism

The mechanism of action of Biotin—CoA ligase involves the ATP-dependent activation of biotin to form biotinyl-AMP and the subsequent transfer of the biotinyl group to CoA, forming biotinyl-CoA. This two-step reaction is essential for the utilization of biotin in various metabolic pathways.

Clinical Significance

Alterations in the activity of Biotin—CoA ligase can lead to metabolic disorders, including problems with fatty acid synthesis and the metabolism of amino acids. Deficiencies in biotin or mutations in the gene encoding Biotin—CoA ligase can result in biotinidase deficiency, a rare genetic disorder that can lead to neurological and cutaneous symptoms if left untreated.

Genetic

The gene encoding Biotin—CoA ligase is highly conserved across different species, highlighting its essential role in metabolism. In humans, this gene has been mapped to a specific chromosome location, and its expression is regulated by nutritional and hormonal factors.

See Also

• Biotin
• Coenzyme A
• Fatty acid metabolism
• Metabolic pathway