Enoyl CoA isomerase

Enoyl-CoA isomerase (ECI), also known as dodecenoyl-CoA isomerase, is an essential enzyme in the metabolic pathway of fatty acid oxidation. This enzyme plays a pivotal role in the beta-oxidation of unsaturated fatty acids, facilitating the rearrangement of cis and trans double bonds in the unsaturated fatty acyl-CoAs. ECI is crucial for the efficient metabolism of both dietary and endogenously synthesized unsaturated fatty acids, thereby contributing to energy production, lipid biosynthesis, and the regulation of cellular lipid composition.

Function

Enoyl-CoA isomerase catalyzes the isomerization of double bonds in unsaturated fatty acyl-CoA substrates. Specifically, it converts cis-Δ^3- and cis-Δ^2-enoyl-CoA esters to their corresponding trans-Δ^2 forms, which are then suitable substrates for further degradation by the beta-oxidation pathway. This reaction is vital for the metabolism of unsaturated fatty acids, which are common in the human diet and are also synthesized by the body. Without ECI, the degradation of unsaturated fatty acids would be inefficient, leading to potential disruptions in energy homeostasis and lipid metabolism.

Structure

Enoyl-CoA isomerase is a mitochondrial enzyme that is widely distributed across different tissues, with high concentrations found in the liver, heart, and skeletal muscle. The enzyme exists in multiple isoforms, which may vary in their activity and specificity for different unsaturated fatty acyl-CoA substrates. The structure of ECI includes a catalytic domain that binds the fatty acyl-CoA substrate and a binding site for coenzyme A, facilitating the isomerization reaction.

Clinical Significance

Alterations in the activity or expression of enoyl-CoA isomerase have been implicated in various metabolic disorders. For instance, deficiencies in ECI can lead to the accumulation of unsaturated fatty acids and their metabolites, which may contribute to the development of fatty liver disease, insulin resistance, and other metabolic syndromes. Furthermore, the enzyme's role in lipid metabolism makes it a potential target for therapeutic interventions aimed at treating obesity, diabetes, and cardiovascular diseases.

Genetic Regulation

The expression of the ECI gene is regulated by various nutritional and hormonal factors, reflecting its role in lipid metabolism. Insulin, glucocorticoids, and thyroid hormones have been shown to influence ECI gene expression, suggesting a complex regulation that adapts to the body's metabolic state. Understanding the genetic regulation of ECI is crucial for elucidating its role in health and disease and for developing strategies to modulate its activity in metabolic disorders.

See Also

• Beta-oxidation
• Fatty acid metabolism
• Lipid metabolism
• Metabolic pathway