Disease relevance of isovaleryl-CoA

• Furthermore, it was postulated that iso-FAs or compounds derived thereof are involved in fruiting body formation in Myxococcus xanthus, since mutants with a reduced level of iso-FA due to a reduced level of the precursor isovaleryl-CoA, are delayed in aggregation and produce only few myxospores [1].
• A biosynthetic pathway to isovaleryl-CoA in myxobacteria: the involvement of the mevalonate pathway [2].

High impact information on isovaleryl-CoA

• Molecular heterogeneity of variant isovaleryl-CoA dehydrogenase from cultured isovaleric acidemia fibroblasts [3].
• By using this assay method with these isolated mitochondria, we have demonstrated a specific deficiency of isovaleryl-CoA dehydrogenase [isovaleryl-CoA: (acceptor) oxidoreductase, EC 1.3.99.10] activity in cultured skin fibroblasts from five patients with isovaleric acidemia [4].
• Isovaleryl-CoA dehydrogenase: demonstration in rat liver mitochondria by ion exchange chromatography and isoelectric focusing [5].
• The resulting mutant IVD had detectable activity with 2-methylbutyryl-CoA and no activity with isovaleryl-CoA [6].
• The dramatic lateral expansion of the binding cavity seen in isovaleryl-CoA dehydrogenase is not observed in IBD [7].

Biological context of isovaleryl-CoA

• The variant human isovaleryl-CoA dehydrogenase gene responsible for type II isovaleric acidemia determines an RNA splicing error, leading to the deletion of the entire second coding exon and the production of a truncated precursor protein that interacts poorly with mitochondrial import receptors [8].
• Molecular cloning and nucleotide sequence of cDNAs encoding the precursors of rat long chain acyl-coenzyme A, short chain acyl-coenzyme A, and isovaleryl-coenzyme A dehydrogenases. Sequence homology of four enzymes of the acyl-CoA dehydrogenase family [9].
• They also establish that differentiated 3T3-L1 adipocytes metabolize leucine like mature adipose tissue and illustrate the roles of the branched chain alpha-ketoacid dehydrogenase and isovaleryl-CoA dehydrogenase in lipogenesis [10].
• Isolation of cDNA clones coding for rat isovaleryl-CoA dehydrogenase and assignment of the gene to human chromosome 15 [11].
• The purified mRNA was used to prepare a plasmid cDNA library which was screened with two oligonucleotide mixtures encoding two peptides in the amino-terminal portion of mature rat isovaleryl-CoA dehydrogenase [11].

Anatomical context of isovaleryl-CoA

• Demonstration of a specific mitochondrial isovaleryl-CoA dehydrogenase deficiency in fibroblasts from patients with isovaleric acidemia [4].
• Rat liver mRNA encoding the cytoplasmic precursor of mitochondrial isovaleryl-CoA dehydrogenase was highly enriched by polysome immunopurification using a polyclonal monospecific antibody [11].
• Southern blot analysis of DNAs from human-rodent somatic cell hybrids with an isolated rat cDNA (2 kbp) assigned the isovaleryl-CoA dehydrogenase gene to the long arm of chromosome 15, region q14----qter [11].
• Postpartum diagnostic tests and/or in vitro assay of isovaleryl-CoA dehydrogenase of [1-14C] isovaleric acid oxidation using amniocytes confirmed that the first two fetuses were affected by isovaleric acidemia, whereas the latter three were unaffected [12].
• METHODS: Isovaleryl-CoA dehydrogenase crude enzyme was prepared by sonicating lymphocytes in peripheral blood [13].

Associations of isovaleryl-CoA with other chemical compounds

• The products of SCA dehydrogenase/butyryl-CoA, MCA dehydrogenase/octanoyl-CoA, and IV dehydrogenase/isovaleryl-CoA reactions were identified as crotonyl-CoA, 2-octenoyl-CoA, and 3-methylcrotonyl-CoA, respectively, using gas chromatography [14].
• This resistance is not due to weak binding: the complex between isovaleryl-CoA dehydrogenase and 2-pentynoyl-CoA shows a Kd of 1.8 microM at pH 7 [15].
• We developed a modified version of the tritium release assay to accurately measure residual isovaleryl-CoA dehydrogenase activity in fibroblasts from patients with both forms of isovaleric acidemia [16].
• In order to begin to identify the role of AidB in the cell, the protein was purified to homogeneity, shown to possess stoichiometric amounts of flavin adenine dinucleotide (FAD), and confirmed to have low levels of isovaleryl-coenzyme A (CoA) dehydrogenase activity [17].
• Isovaleryl-CoA dehydrogenase (IVD) is a homotetrameric flavoenzyme, which catalyzes the conversion of isovaleryl-CoA to 3-methylcrotonyl-CoA and transfers electrons to the electron-transferring flavoprotein, and is a member of the acyl-CoA dehydrogenase (ACD) enzyme family [18].

Gene context of isovaleryl-CoA

• The E254D mutant IVD had residual activity for isovaleryl-CoA, and its spectrum was altered compared to that of the wild type [19].
• Analyses of the assay conditions suggest a rationale for the lack of activity previously reported for some substrates (e.g. isovaleryl-CoA) for the (His)6pro-PAHX [20].
• The apparent binding constant (K(D app)) of the recombinant IVD determined spectrally for isovaleryl-CoA was 0.34 microM [21].
• Metabolism of leucine in fibroblasts from patients with deficiencies in each of the major catabolic enzymes: branched-chain ketoacid dehydrogenase, isovaleryl-CoA dehydrogenase, 3-methylcrotonyl-CoA carboxylase, 3-methylglutaconyl-CoA hydratase, and 3-hydroxy-3-methylglutaryl-CoA lyase [22].
• Short-chain acyl-CoA (SCADH), medium-chain acyl-CoA (MCADH) and isovaleryl-CoA (IVDH) dehydrogenases were severely and irreversibly inactivated by MCPA-CoA, while 2-methyl-branched chain acyl-CoA dehydrogenase (2-meBCADH) was only slowly and mildly inactivated [23].

Analytical, diagnostic and therapeutic context of isovaleryl-CoA

• Establishment of a practical enzymatic assay method for determination of isovaleryl-CoA dehydrogenase activity using high-performance liquid chromatography [13].

References