Activation of glycolysis and apoptosis in glycogen storage disease type Ia.
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.
Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA.
Baodong
B
Sun
Songtao
S
Li
Liu
L
Yang
Tirupapuliyur
T
Damodaran
Dev
D
Desai
Anna Mae
AM
Diehl
Oscar
O
Alzate
Dwight D
DD
Koeberl
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics; D005953:Glycogen Storage Disease Type I / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D006019:Glycolysis / Q000235:genetics*; D008099:Liver / Q000473:pathology; D051379:Mice
D005987:Glyceraldehyde-3-Phosphate Dehydrogenases