Biswas S, Ray M, Misra S, Dutta D P, Ray S
Department of Biological Chemistry, Indian Association for the Cultivation of Science, Calcutta 700 032, India.
Biochem J. 1997 Apr 15;323 ( Pt 2)(Pt 2):343-8. doi: 10.1042/bj3230343.
The effect of methylglyoxal on the oxygen consumption of mitochondria of both normal and leukaemic leucocytes was tested by using different respiratory substrates and complex specific artificial electron donors and inhibitors. The results indicate that methylglyoxal strongly inhibits mitochondrial respiration in leukaemic leucocytes, whereas, at a much higher concentration, methylglyoxal fails to inhibit mitochondrial respiration in normal leucocytes. Methylglyoxal strongly inhibits ADP-stimulated alpha-oxoglutarate and malate plus NAD+-dependent respiration, whereas, at a higher concentration, methylglyoxal fails to inhibit succinate and alpha-glycerophosphate-dependent respiration. Methylglyoxal also fails to inhibit respiration which is initiated by duroquinone and cannot inhibit oxygen consumption when the N,N,N', N'-tetramethyl-p-phenylenediamine by-pass is used. NADH oxidation by sub-mitochondrial particles of leukaemic leucocytes is also inhibited by methylglyoxal. Lactaldehyde, a catabolite of methylglyoxal, can exert a protective effect on the inhibition of leukaemic leucocyte mitochondrial respiration by methylglyoxal. Methylglyoxal also inhibits l-lactic acid formation by intact leukaemic leucocytes and critically reduces the ATP level of these cells, whereas methylglyoxal has no effect on normal leucocytes. We conclude that methylglyoxal inhibits glycolysis and the electron flow through mitochondrial complex I of leukaemic leucocytes. This is strikingly similar to our previous studies on mitochondrial respiration, glycolysis and ATP levels in Ehrlich ascites carcinoma cells [Ray, Dutta, Halder and Ray (1994) Biochem. J. 303, 69-72; Halder, Ray and Ray (1993) Int. J. Cancer 54, 443-449], which strongly suggests that the inhibition of electron flow through complex I of the mitochondrial respiratory chain and inhibition of glycolysis by methylglyoxal may be common characteristics of all malignant cells.
通过使用不同的呼吸底物以及复合物特异性人工电子供体和抑制剂，测试了甲基乙二醛对正常白细胞和白血病白细胞线粒体氧消耗的影响。结果表明，甲基乙二醛强烈抑制白血病白细胞的线粒体呼吸，而在高得多的浓度下，甲基乙二醛未能抑制正常白细胞的线粒体呼吸。甲基乙二醛强烈抑制ADP刺激的α-酮戊二酸和苹果酸加NAD⁺依赖性呼吸，而在较高浓度下，甲基乙二醛未能抑制琥珀酸和α-磷酸甘油依赖性呼吸。甲基乙二醛也未能抑制由杜醌引发的呼吸，并且当使用N，N，N'，N'-四甲基对苯二胺旁路时不能抑制氧消耗。白血病白细胞亚线粒体颗粒的NADH氧化也受到甲基乙二醛的抑制。甲基乙二醛的分解代谢产物乳醛可以对甲基乙二醛抑制白血病白细胞线粒体呼吸发挥保护作用。甲基乙二醛还抑制完整白血病白细胞的l-乳酸形成，并严重降低这些细胞的ATP水平，而甲基乙二醛对正常白细胞没有影响。我们得出结论，甲基乙二醛抑制白血病白细胞的糖酵解和通过线粒体复合物I的电子流。这与我们之前关于艾氏腹水癌细胞线粒体呼吸、糖酵解和ATP水平的研究[Ray，Dutta，Halder和Ray（1994年）《生物化学杂志》303卷，69 - 72页；Halder，Ray和Ray（1993年）《国际癌症杂志》54卷，443 - 449页]惊人地相似，这强烈表明通过线粒体呼吸链复合物I的电子流抑制和甲基乙二醛对糖酵解的抑制可能是所有恶性细胞的共同特征。
