Isovaleryl-CoA dehydrogenase

Isovaleryl-CoA dehydrogenase (IVD) is an enzyme that in humans is encoded by the IVD gene. This enzyme is a part of the fatty acid metabolism pathway and plays a crucial role in the metabolism of leucine, an essential amino acid. Isovaleryl-CoA dehydrogenase catalyzes the third step in leucine catabolism, which involves the oxidative decarboxylation of isovaleryl-CoA to 3-methylcrotonyl-CoA.

Function

Isovaleryl-CoA dehydrogenase is a mitochondrial enzyme that belongs to the acyl-CoA dehydrogenase family. It is involved in the catabolism of leucine, a process that contributes to the production of energy in the form of adenosine triphosphate (ATP) within cells. The enzyme's action facilitates the removal of a carbon group from isovaleryl-CoA, converting it into 3-methylcrotonyl-CoA, a step that is critical for the continuation of leucine degradation towards acetyl-CoA and acetoacetate, both of which are important substrates for the Krebs cycle and ketogenesis, respectively.

Clinical Significance

Mutations in the IVD gene are associated with Isovaleric acidemia, a rare inborn error of metabolism characterized by a deficiency of the isovaleryl-CoA dehydrogenase enzyme. This condition leads to an accumulation of isovaleric acid in the blood, urine, and tissues, causing a range of symptoms from mild to severe, including poor feeding, vomiting, seizures, and possibly death if untreated. Early diagnosis and management, which may include dietary restrictions and carnitine supplementation, are crucial for affected individuals.

Genetic

The IVD gene is located on chromosome 15q14-15 in humans and consists of 15 exons. Variants in this gene can lead to partial or complete deficiency of the isovaleryl-CoA dehydrogenase enzyme, underlying the pathogenesis of Isovaleric acidemia.

Diagnosis

Diagnosis of Isovaleric acidemia typically involves biochemical tests that detect elevated levels of isovaleric acid in the blood or urine. Genetic testing can confirm mutations in the IVD gene, providing a definitive diagnosis.

Treatment

Treatment for Isovaleric acidemia focuses on managing symptoms and preventing metabolic crises. This may involve dietary management to restrict leucine intake, supplementation with glycine or carnitine to enhance the excretion of isovaleric acid, and emergency treatment protocols during illness or metabolic stress.

See Also

• Fatty acid metabolism
• Leucine
• Inborn error of metabolism
• Krebs cycle
• Ketogenesis