Acyl phosphatase activity of NO-inhibited glyceraldehyde-3-phosphate dehydrogenase (GAPDH): a potential mechanism for uncoupling glycolysis from ATP generation in NO-producing cells.
Treatment of glyceraldehyde-3-phosphate - dehydrogenase (GA (GAPDH) with the NO donors S-nitrosoglutathione, 3-morpholinosydnonimine or diethylamine NONOate (diethylamine diazeniumdiolate) in vitro, inhibited its dehydrogenase activity and induced its acyl phosphatase activity. NO-producing cells, in turn, exhibited reduced GAPDH activity, increased glycolysis, and decreased ATP content, synthesis and turnover. These cellular alterations could be explained by the uncoupling of glycolytic flux from substrate level phosphorylation by the acyl phosphatase activity of NO-modified GAPDH.
Albina
J E
JE
Department of Surgery, Division of Surgical Research, NAB-2, Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903, USA. Jorge_Albina@Brown.edu
Mastrofrancesco
B
B
Reichner
J S
JS
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D004734:Energy Metabolism; D005947:Glucose / Q000378:metabolism; D005978:Glutathione / Q000031:analogs & derivatives / Q000494:pharmacology; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects*; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D009132:Muscles / Q000201:enzymology; D009569:Nitric Oxide / Q000494:pharmacology*; D009603:Nitroso Compounds / Q000494:pharmacology; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D010766:Phosphorylation; D011817:Rabbits; D051381:Rats; D011916:Rats, Inbred F344; D026422:S-Nitrosoglutathione; D014475:Uncoupling Agents / Q000494:pharmacology
D009603:Nitroso Compounds; D014475:Uncoupling Agents; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; D000255:Adenosine Triphosphate; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D010744:Phosphoric Monoester Hydrolases; D005978:Glutathione; D005947:Glucose