Mateo R B, Reichner J S, Mastrofrancesco B, Kraft-Stolar D, Albina J E
Department of Surgery, Rhode Island Hospital, Providence.
Am J Physiol. 1995 Mar;268(3 Pt 1):C669-75. doi: 10.1152/ajpcell.1995.268.3.C669.
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.
关于一氧化氮（NO）在细胞葡萄糖代谢调节中的作用，已出现相互矛盾的证据。虽然它可通过糖酵解和己糖磷酸旁路增强巨噬细胞及其他细胞对葡萄糖的摄取和利用，但NO也会抑制甘油醛-3-磷酸脱氢酶，该酶催化这两条途径产生的中间产物的代谢。实际上，有人提出NO通过抑制甘油醛-3-磷酸脱氢酶的活性来调节糖酵解通量。为确定这些明显相互矛盾的作用的相对影响，研究了外源性或内源性NO对巨噬细胞葡萄糖代谢不同方面的影响。细胞活化增加了NO的产生、最大甘油醛-3-磷酸脱氢酶活性以及通过糖酵解和己糖磷酸旁路的葡萄糖代谢。内源性产生的或由S-亚硝基-N-乙酰青霉胺（>500微摩尔）产生的NO降低了培养物中最大甘油醛-3-磷酸脱氢酶活性。仅在培养物中活细胞明显减少的情况下，最大甘油醛-3-磷酸脱氢酶的抑制才与乳酸积累减少同时出现。当被NO适度抑制时，最大甘油醛-3-磷酸脱氢酶活性似乎并非葡萄糖代谢的限速因素。甘油醛-3-磷酸脱氢酶的深度抑制与细胞死亡之间的潜在因果关系仍有待确定。
