Reversion of the Maple Syrup Urine Disease Phenotype of Impaired Branched Chain α-Ketoacid Dehydrogenase Complex Activity in Fibroblasts from an Affected Child

Autor:	Dean J. Danner, W J Herring, Stuart Litwer
Rok vydání:	1989
Předmět:	Mutation Maple syrup urine disease nutritional and metabolic diseases Dehydrogenase Cell Biology Transfection Biology Mitochondrion medicine.disease medicine.disease_cause Biochemistry Molecular biology Acyltransferase Complementary DNA medicine Molecular Biology Gene
Zdroj:	Journal of Biological Chemistry. 264:14597-14600
ISSN:	0021-9258
DOI:	10.1016/s0021-9258(18)63735-4
Popis:	Branched chain alpha-ketoacid dehydrogenase is a heteroprotein complex of mitochondria and commits the branched chain alpha-ketoacids to their catabolic fate. Inherited nuclear mutations in humans decrease the activity of this complex and result in maple syrup urine disease. Here we demonstrate the restoration of branched chain alpha-ketoacid dehydrogenase activity to fibroblasts from a child with this disorder by transfection with a cDNA for the prebranched chain acyltransferase. Prior to transfection these fibroblasts contained the prebranched chain acyltransferase gene but failed to transcribe the gene and thus lacked the protein. Regulation of the restored complex by phosphorylation mechanisms resembles that of wild-type cells. These results describe a human cell modeling system for testing engineered proteins and support the possibility of gene replacement therapy for this human disorder.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::5f126fdb59fa996844609509b651df84 https://doi.org/10.1016/s0021-9258(18)63735-4 Zobrazit plný text záznamu