Enoyl-CoA hydratase

Enoyl-CoA hydratase (ECH) is an enzyme that plays a crucial role in the metabolism of fatty acids by catalyzing the hydration of enoyl-CoA to 3-hydroxyacyl-CoA. This reaction is a key step in the beta oxidation pathway, which is the process by which fatty acids are broken down to generate acetyl-CoA, a vital molecule for energy production in cells. Enoyl-CoA hydratase exists in two forms: a short-chain enzyme active on acyl-CoA derivatives with a chain length of four to six carbon atoms, and a long-chain enzyme that acts on substrates with chain lengths of eight to sixteen carbon atoms.

Function

Enoyl-CoA hydratase catalyzes the second step in the beta oxidation cycle. Specifically, it converts the trans double bond between the second and third carbon atoms of an unsaturated acyl-CoA to a hydroxyl group, resulting in a 3-hydroxyacyl-CoA. This reaction is essential for the degradation of fatty acids to produce energy, particularly during periods when carbohydrates are scarce.

Structure

The enzyme is found in both the mitochondria and peroxisomes, indicating its importance in cellular energy metabolism across different organelles. The mitochondrial and peroxisomal forms of the enzyme are encoded by separate genes, which reflects the enzyme's evolutionary adaptation to specific cellular environments and functions.

Mechanism

Enoyl-CoA hydratase operates through a covalent catalysis mechanism. The enzyme has an active site that binds to the enoyl-CoA substrate. A glutamate residue in the active site then acts as a base, abstracting a proton from water, which is then added to the second carbon of the enoyl-CoA. Simultaneously, a histidine residue donates a proton to the third carbon, completing the hydration of the double bond to form 3-hydroxyacyl-CoA.

Clinical Significance

Mutations in the genes encoding enoyl-CoA hydratase can lead to metabolic disorders, including Leigh syndrome and multiple acyl-CoA dehydrogenase deficiency (MADD). These conditions are characterized by impaired energy production and accumulation of fatty acids and their derivatives, which can be toxic to cells.

See Also

• Beta oxidation
• Fatty acid metabolism
• Acetyl-CoA
• Mitochondria
• Peroxisomes