Abstract
IVD is a mitochondrial flavoprotein, a tetramer of 43 kDa subunits, which catalyzes the third reaction in leucine metabolism. Hereditary deficiency of IVD causes isovaleric acidemia, one of the more common inherited organic acidemias, characterized by recurrent episodes of vomiting, ketoacidosis, lethargy and sweaty feet odor. Extensive molecular heterogeneity, including at least five distinct variant alleles, has been shown on the basis of the presence or absence of immunoprecipitable variant IVDs and their sizes (PNAS 82:7081, 1985). As a first step in the study of the molecular basis of isovaleric acidemia, we have isolated a cDNA clone encoding rat IVD. First, we highly purified the mRNA encoding IVD from rat liver by polysome immunopurification using polyclonal, monospecific antibody. A cDNA library, enriched for IVD, was prepared using the purified mRNA, and screened by colonly hybridization using two oligonucleotides (17-mer and 15-mer) corresponding to the portions of the NH2-terminal amino acid sequence. Numerous positive cDNA clones were isolated. One of them contained a 54 bp portion which perfectly matched an 18 amino acid peptide from the amino terminus of pure rat IVD, thereby positively identifying the clone as that of rat IVD. This cDNA extends 100 bp towards the 5′ end, indicating that it contains the entire sequence for the leader peptide (2 kDa). Screening of human cDNA libraries for IVD cDNA is in progress.
Article PDF
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Matsubara, Y., Kraus, J., Glassberq, R. et al. MOLECULAR CLONING OF cDNA ENCODING RAT ISOVALERYL-CoA DEHYDROGENASE (IVD). Pediatr Res 21 (Suppl 4), 292 (1987). https://doi.org/10.1203/00006450-198704010-00747
Issue Date:
DOI: https://doi.org/10.1203/00006450-198704010-00747