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 N O donors S-nitrosoglutathione, 3-morpholinusydnonimine or diethylamine NONO ate (diethylamine diazeniumdiolate) in vitro, inhibited its dehydrogenase a ctivity and induced its acyl phosphatase activity. NO-producing cells, in t urn, exhibited reduced GAPDH activity, increased glycolysis, and decreased ATP content, synthesis and turnover. These cellular alterations could be ex plained by the uncoupling of glycolytic flux from substrate level phosphory lation by the acyl phosphatase activity of NO-modified GAPDH.