Journal of Inherited Metabolic Disease

, Volume 14, Issue 1, pp 37–44

Altered phosphorylation state of branched-chain 2-Oxo acid dehydrogenase in a branched-chain acyltransferase deficient human fibroblast cell line

  • R. S. Eisenstein
  • G. Hoganson
  • R. H. Miller
  • A. E. Harper
Article

DOI: 10.1007/BF01804386

Cite this article as:
Eisenstein, R.S., Hoganson, G., Miller, R.H. et al. J Inherit Metab Dis (1991) 14: 37. doi:10.1007/BF01804386

Summary

The abundance and phosphorylation state of the polypeptide constitutents of the human branched-chain 2-oxo acid dehydrogenase complex were examined in mitochondria from normal and maple syrup urine disease (MSUD) fibroblasts. In normal fibroblast mitochondria two forms of the E subunit were observed: non-phosphorylated (E) and phosphorylated (E1α−P). About 40–50% of E was present as E1α−P. The ability to quantitate the two forms of E permitted examination of the association between decreased capacity to oxidize branched-chain 2-oxo acids and the phosphorylation state of E.

Changes in phosphorylation state of E were observed in MSUD fibroblasts as compared to control cells. Of particular interest was the absence of E1α−P in an MSUD fibroblast line which lacked the dihydrolipoyl acyltransferase (E2) subunit of the dehydrogenase complex. In two MSUD cell lines deficient in E, the abundance of E1α−P appeared to be preferentially reduced. A fourth MSUD cell line contained normal quantities of E3, E2 and both forms of the E polypeptide. Our results indicate that alterations in the abundance of dehydrogenase complex polypeptides in MSUD fibroblasts may influence the phosphorylation state of the E polypeptide. They demonstrate the potential for examining simultaneously mutations which affect both the catalytic and regulatory components of the dehydrogenase complex.

Copyright information

© SSIEM and Kluwer Academic Publishers 1991

Authors and Affiliations

  • R. S. Eisenstein
    • 1
  • G. Hoganson
    • 3
  • R. H. Miller
    • 2
  • A. E. Harper
    • 1
    • 2
  1. 1.Department of BiochemistryUniversity of Wisconsin-MadisonMadisonUSA
  2. 2.Department of Nutritional SciencesUniversity of Wisconsin-MadisonMadisonUSA
  3. 3.Departments of Pediatrics and GeneticsUniversity of Illinois at ChicagoChicagoUSA
  4. 4.Division of ToxicologyMassachusetts Institute of TechnologyCambridgeUSA
  5. 5.Medical DepartmentRoss LaboratoriesColumbusUSA

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