Methylglutaconyl-CoA hydratase

Methylglutaconyl-CoA hydratase (MGCH), also known as 3-methylglutaconyl-CoA hydratase, is an enzyme that in humans is encoded by the AUH gene. This enzyme is involved in the Leucine degradation pathway, specifically in the metabolism of 3-methylglutaconic acid. MGCH catalyzes the hydration of 3-methylglutaconyl-CoA to 3-hydroxy-3-methylglutaryl-CoA, a critical step in the breakdown and utilization of leucine for energy.

Function

Methylglutaconyl-CoA hydratase plays a crucial role in the metabolic pathway of leucine, an essential Amino acid. The enzyme's action facilitates the conversion of 3-methylglutaconyl-CoA, a potentially toxic compound, into a more readily metabolized form. This process is vital for the maintenance of cellular energy levels and the prevention of the accumulation of harmful substances within the cell.

Genetic and Molecular Basis

The AUH gene, located on human chromosome 9q22.31, encodes the MGCH enzyme. Mutations in the AUH gene can lead to deficient activity of MGCH, resulting in metabolic disorders such as 3-Methylglutaconic aciduria type I. This condition is characterized by the accumulation of 3-methylglutaconic acid and related metabolites in the body, leading to various clinical manifestations, including developmental delay, neurological deficits, and metabolic acidosis.

Clinical Significance

Understanding the function and regulation of MGCH is crucial for the diagnosis and treatment of metabolic disorders involving leucine degradation. The identification of mutations in the AUH gene has facilitated the development of genetic testing for 3-Methylglutaconic aciduria type I, allowing for early diagnosis and management of the condition. Research into MGCH and its associated pathways may also provide insights into novel therapeutic approaches for treating metabolic diseases.

See Also

• Leucine
• Metabolism
• Amino acid
• 3-Methylglutaconic aciduria
• Genetic testing