Impact of nitric oxide on macrophage glucose metabolism and glyceraldehyde-3-phosphate dehydrogenase activity.
Conflicting evidence has been presented regarding the role of nitric oxide (NO) in the regulation of cellular glucose metabolism. While it enhances glucose uptake and utilization through glycolysis and the hexose monophosphate shunt in macrophages and other cells, NO also inhibits glyceraldehyde-3-phosphate dehydrogenase, an enzyme catalyzing the metabolism of intermediates generated by both pathways. Indeed, it has been proposed that NO modulates glycolytic flux by suppressing glyceraldehyde-3-phosphate dehydrogenase activity. To establish the relative impact of these apparently incompatible actions, the effects of exogenous or endogenous NO on different aspects of glucose metabolism in macrophages were investigated. Cell activation increased NO production, maximal glyceraldehyde-3-phosphate dehydrogenase activity, and glucose metabolism through glycolysis and the hexose monophosphate shunt. NO generated endogenously or from S-nitroso-N-acetylpenicillamine (> 500 microM) reduced maximal glyceraldehyde-3-phosphate dehydrogenase activity in culture. The suppression of maximal glyceraldehyde-3-phosphate dehydrogenase coincided with decreased lactate accumulation only in concert with a marked loss of viable cells in the cultures. The maximal glyceraldehyde-3-phosphate dehydrogenase activity did not appear to be rate limiting for glucose metabolism when moderately inhibited by NO. A potential causal relationship between profound glyceraldehyde-3-phosphate dehydrogenase inhibition and cell death remains to be established.
Mateo
R B
RB
Department of Surgery, Rhode Island Hospital, Providence.
Reichner
J S
JS
Mastrofrancesco
B
B
Kraft-Stolar
D
D
Albina
J E
JE
D000594:Amino Acid Oxidoreductases / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D003470:Culture Media; D005947:Glucose / Q000378:metabolism*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism*; D006019:Glycolysis; D007371:Interferon-gamma / Q000494:pharmacology; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology*; D019001:Nitric Oxide Synthase; D010427:Pentose Phosphate Pathway; D051381:Rats
D003470:Culture Media; D007773:Lactates; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D019344:Lactic Acid; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D000594:Amino Acid Oxidoreductases; D005947:Glucose