Disease relevance of C03069

• Acyl-coenzyme A carboxylases. Homologous 3-methylcrotonyl-CoA and geranyl-CoA carboxylases from Pseudomonas citronellolis [1].
• Investigations of the structure of 3-methylcrotonyl-CoA carboxylase from Achromobacter [2].

High impact information on C03069

• Cloning of the human MCCA and MCCB genes and mutations therein reveal the molecular cause of 3-methylcrotonyl-CoA: carboxylase deficiency [3].
• Based upon sequences of biotin enzymes that use substrates structurally related to 3-methylcrotonyl-CoA, we isolated the MCC-B cDNA and gene of Arabidopsis [4].
• Isovaleric acidemia is a rare inborn error of metabolism caused by a deficiency of isovaleryl-CoA dehydrogenase (IVD), a nucleus-encoded, homotetrameric, mitochondrial flavoenzyme that catalyzes the conversion of isovaleryl-CoA to 3-methylcrotonyl-CoA [5].
• Isovaleryl-CoA dehydrogenase (IVD) is a homotetrameric mitochondrial flavoenzyme which catalyzes the conversion of isovaleryl-CoA to 3-methylcrotonyl-CoA [6].
• Here, we tested whether 3-methylcrotonyl-CoA carboxylase (MCC) mutant flies exhibit gene expression patterns and heat susceptibility similar to that in HCS-deficient Drosophila [7].

Chemical compound and disease context of C03069

• By inactivation of different concentrations of 3-methylcrotonyl-CoA carboxylase from Achromobacter IVS with a fixed concentration of iodoacetamide, it was demonstrated that the degree of dissociation of the complex is considerably lower in the presence of 3-methylcrotonyl-CoA [8].

Biological context of C03069

• It was shown by reassociation experiments under different conditions that probably an initial complex, AxBy is formed, possessing a binding site for 3-methylcrotonyl-CoA [2].
• Infantile mitochondrial DNA depletion syndrome associated with methylmalonic aciduria and 3-methylcrotonyl-CoA and propionyl-CoA carboxylase deficiencies in two unrelated patients: a new phenotype of mtDNA depletion syndrome [9].

Associations of C03069 with other chemical compounds

• Plants contain multiple biotin enzymes: discovery of 3-methylcrotonyl-CoA carboxylase, propionyl-CoA carboxylase and pyruvate carboxylase in the plant kingdom [10].
• Kinetic studies of the 3-methylcrotonyl-CoA carboxylase reaction with variable concentrations of two substrates confirmed that ATP and HCO3- bind sequentially to the enzyme and that ATP and 3-methylcrotonyl-CoA bind in ping-pong fashion [11].
• A coupled assay has been developed using 3-methylcrotonyl-CoA and NaH14CO3 which permits the detection of deficiencies of 3-methylcrotonyl-CoA carboxylase, 3-methylglutaconyl-CoA hydratase and 3-hydroxy-3-methylglutaryl CoA-lyase [12].

Gene context of C03069

• Isovaleryl-CoA dehydrogenase (IVD) is a homotetrameric flavoenzyme which catalyzes the conversion of isovaleryl-CoA to 3-methylcrotonyl-CoA [13].
• The inhibition of 3-methylcrotonyl-CoA carboxylase by sulfhydryl and arginyl modifying reagents could be partly alleviated by the substrates ATP and 3-methylcrotonyl-CoA, which suggests that sulfhydryl and arginyl residues may be involved in catalysis [11].
• We studied the effect of biotin on the genetic expression of rat liver mitochondrial carboxylases: pyruvate carboxylase (PC), propionyl-CoA carboxylase (PCC), and 3-methylcrotonyl-CoA carboxylase (MCC) [14].
• Isovaleryl-CoA dehydrogenase (IVD) is a flavoenzyme, which catalyzes the conversion of isovaleryl-CoA to 3-methylcrotonyl-CoA in the leucine catabolism pathway and transfers electrons to the electron-transferring flavoprotein (ETF) [15].

Analytical, diagnostic and therapeutic context of C03069

• 3-Methylcrotonyl-CoA produced in the samples was separated by HPLC and detected using an ultraviolet spectrophotometer [16].
• We established a direct assay method to detect 3-methylcrotonyl-CoA (MC-CoA) production using high-performance liquid chromatography (HPLC) [16].

References