Isovaleryl-CoA dehydrogenase: Difference between revisions

Revision as of 11:17, 15 February 2025

Isovaleryl-CoA dehydrogenase

File:Isovaleryl-CoA dehydrogenase 1ivh.jpg

Structure of 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

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-'''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.
+{{DISPLAYTITLE:Isovaleryl-CoA dehydrogenase}}
+== Isovaleryl-CoA dehydrogenase ==
+[[File:Isovaleryl-CoA_dehydrogenase_1ivh.jpg|thumb|right|300px|Structure of 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 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.
+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.
-== 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 ==
+== Structure ==
-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.
+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.
-== Diagnosis ==
+== Clinical significance ==
-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.
+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.
-== Treatment ==
+== Related enzymes ==
-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.
+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)
-== See Also ==
+== Related pages ==
-* [[Fatty acid metabolism]]
+* [[Leucine metabolism]]
-* [[Leucine]]
+* [[Acyl-CoA dehydrogenase family]]
-* [[Inborn error of metabolism]]
+* [[Isovaleric acidemia]]
-* [[Krebs cycle]]
+* [[Electron transport chain]]
-* [[Ketogenesis]]
 [[Category:Enzymes]]
-[[Category:Human proteins]]
 [[Category:Metabolism]]
-{{Medicine-stub}}
+[[Category:Dehydrogenases]]