Activation of glycolysis and apoptosis in glycogen storage disease type Ia.

Journal Article (Journal Article)

The deficiency of glucose-6-phosphatase (G6Pase) underlies glycogen storage disease type Ia (GSD-Ia, von Gierke disease; MIM 232200), an autosomal recessive disorder of metabolism associated with life-threatening hypoglycemia, growth retardation, renal failure, hepatic adenomas, and hepatocellular carcinoma. Liver involvement includes the massive accumulation of glycogen and lipids due to accumulated glucose-6-phosphate and glycolytic intermediates. Proteomic analysis revealed elevations in glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and other enzymes involved in glycolysis. GAPDH was markedly increased in murine G6Pase-deficient hepatocytes. The moonlighting role of GAPDH includes increasing apoptosis, which was demonstrated by increased TUNEL assay positivity and caspase 3 activation in the murine GSD-Ia liver. These analyses of hepatic involvement in GSD-Ia mice have implicated the induction of apoptosis in the pathobiology of GSD-Ia.

Full Text

Duke Authors

Cited Authors

  • Sun, B; Li, S; Yang, L; Damodaran, T; Desai, D; Diehl, AM; Alzate, O; Koeberl, DD

Published Date

  • August 2009

Published In

Volume / Issue

  • 97 / 4

Start / End Page

  • 267 - 271

PubMed ID

  • 19419892

Electronic International Standard Serial Number (EISSN)

  • 1096-7206

Digital Object Identifier (DOI)

  • 10.1016/j.ymgme.2009.04.003


  • eng

Conference Location

  • United States