Mammalian α-keto acid dehydrogenase complexes: Gene regulation and genetic defects

M. S. Patel, R. A. Harris

Research output: Contribution to journalReview article

63 Scopus citations


Recent application of the tools of molecular biology has provided insight with respect to the structure, regulation, and defects of the genes encoding the PDC and the BCKADC. cDNAs for the α-KGDC have only recently been cloned. Evidence for long-term regulation of the expression of the subunits of the PDC and the BCKADC has been obtained. Detailed analyses of the promoter- regulatory regions of the genes encoding the individual subunits of these complexes have provided leads as to molecular mechanisms involved. Evidence for coordinated regulation of expression of the subunits of the complexes has been obtained under some conditions but not others. Except for the PDC E1α(X) promoter, the other promoters of the genes encoding PDC and BCKADC components are TATA-less with characteristics of housekeeping genes. Most cases of PDC deficiency, which produces lactic acidosis, are caused by defects in the coding region of the E1α subunit. In contrast, gene defects that cause maple syrup urine disease are more heterogeneous, involving errors in any one of the subunits of the BCKADC. α-KGDC deficiency has been reported but specific mutations have not been identified. Future work is expected to include detailed studies of the genes encoding the protein kinases and phosphatases that specifically regulate the PDC and the BCKADC by covalent modification.

Original languageEnglish (US)
Pages (from-to)1164-1172
Number of pages9
JournalFASEB Journal
Issue number12
StatePublished - Jan 1 1995



  • branched-chain α-keto acid dehydrogenase complex
  • gene organization
  • genetic defects
  • pyruvate dehydrogenase complex

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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