Molecular basis of isovaleric acidemia and medium-chain acyl-CoA dehydrogenase deficiency.

Abstract

Our early study of isovaleric acidemia (IVA) indicated that isovaleryl-CoA is dehydrogenated by an enzyme that is specific for isovaleryl-CoA. We subsequently identified and purified isovaleryl-CoA dehydrogenase (IVD) and 2-methyl-branched chain acyl-CoA dehydrogenase, which were previously unknown. We also purified and characterized three previously known acyl-CoA dehydrogenases. Five acyl-CoA dehydrogenases share similar molecular features and reaction mechanisms, indicating a close evolutionary relationship. Using the tritium release assay and [35S]methionine labeling/immunoprecipitation, we showed that IVA is due to a mutation of IVD. We also demonstrated that there are at least 5 distinct forms of mutant IVD, indicating an extensive molecular heterogeneity. Furthermore, we cloned cDNAs encoding IVD and medium-chain acyl-CoA dehydrogenases. The comparison of their complete primary sequences revealed a high degree of homology, indicating that these enzymes belong to a gene family, the acyl-CoA dehydrogenase family.

• Authors: K Tanaka, Y Ikeda, Y Matsubara, D B Hyman
• Journal: Enzyme (Enzyme) Vol. 38 Issue 1-4 Pg. 91-107 ( 1987) ISSN: 0013-9432 [Print] Switzerland
• PMID: 3326738 (Publication Type: Journal Article, Review)

Chemical References

• DNA, Circular
• Hemiterpenes
• Pentanoic Acids
• Valerates
• isovaleric acid
• Oxidoreductases
• Acyl-CoA Dehydrogenases
• Oxidoreductases Acting on CH-CH Group Donors
• Isovaleryl-CoA Dehydrogenase

Topics

• Acyl-CoA Dehydrogenases (deficiency, genetics, isolation & purification)
• Amino Acid Sequence
• Base Sequence
• DNA, Circular (genetics)
• Hemiterpenes
• Humans
• Isovaleryl-CoA Dehydrogenase
• Metabolism, Inborn Errors (blood, genetics)
• Molecular Sequence Data
• Mutation
• Oxidoreductases (deficiency, genetics, isolation & purification)
• Oxidoreductases Acting on CH-CH Group Donors
• Pentanoic Acids (blood)
• Protein Biosynthesis
• Sequence Homology, Nucleic Acid
• Valerates (blood)