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

Abstract

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.

• Authors: Baodong Sun, Songtao Li, Liu Yang, Tirupapuliyur Damodaran, Dev Desai, Anna Mae Diehl, Oscar Alzate, Dwight D Koeberl
• Journal: Molecular genetics and metabolism (Mol Genet Metab) Vol. 97 Issue 4 Pg. 267-71 (Aug 2009) ISSN: 1096-7206 [Electronic] United States
• PMID: 19419892 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glyceraldehyde-3-Phosphate Dehydrogenases

Topics

• Animals
• Apoptosis (genetics)
• Glyceraldehyde-3-Phosphate Dehydrogenases (genetics)
• Glycogen Storage Disease Type I (metabolism, pathology, physiopathology)
• Glycolysis (genetics)
• Liver (pathology)
• Mice