Isovaleryl-CoA dehydrogenase

Isovaleryl-CoA dehydrogenase is an enzyme that plays a crucial role in the metabolism of branched-chain amino acids, specifically leucine. It is a member of the acyl-CoA dehydrogenase family, which is involved in the beta-oxidation of fatty acids.

Function

Isovaleryl-CoA dehydrogenase catalyzes the third step in the breakdown of leucine, converting isovaleryl-CoA to 3-methylcrotonyl-CoA. This reaction involves the removal of electrons from isovaleryl-CoA, which are transferred to the electron transfer flavoprotein (ETF), ultimately contributing to the electron transport chain and ATP production.

Structure

The enzyme is a homotetramer, meaning it consists of four identical subunits. Each subunit contains a flavin adenine dinucleotide (FAD) cofactor, which is essential for its dehydrogenase activity. The structure of isovaleryl-CoA dehydrogenase has been elucidated through X-ray crystallography, revealing details about its active site and substrate binding.

Clinical significance

Deficiency in isovaleryl-CoA dehydrogenase activity leads to a metabolic disorder known as isovaleric acidemia. This condition is characterized by the accumulation of isovaleric acid, which can cause severe metabolic acidosis, a distinctive "sweaty feet" odor, and neurological complications. Early diagnosis and management are crucial to prevent serious outcomes.

Related enzymes

Isovaleryl-CoA dehydrogenase is part of a larger family of acyl-CoA dehydrogenases, which includes:

• Medium-chain acyl-CoA dehydrogenase (MCAD)
• Short-chain acyl-CoA dehydrogenase (SCAD)
• Very long-chain acyl-CoA dehydrogenase (VLCAD)

Related pages

• Leucine metabolism
• Acyl-CoA dehydrogenase family
• Isovaleric acidemia
• Electron transport chain