Shimamoto N, Goto N, Hirata M
Nihon Yakurigaku Zasshi. 1982 Aug;80(2):137-45.
Effects of CV-2619 and ubiquinone-10 (Q-10) on the energy metabolism of red blood cells (RBC) of Sprague Dawley rats were studied in the presence or absence of NaF. NaF (0.3--10 mM) dose-dependently decreased the ATP and lactate contents of the RBC. In the presence of NaF (1.5 mM), ATP content decreased to about 30% of the control. Phosphofructokinase (PFK) was markedly activated, while glyceraldehydephosphate dehydrogenase (GAPDH) and enolase were inhibited by NaF. Thus, the decrease in ATP by NaF might be attributed to retarded glycolysis due to inhibition of the latter two enzymes. The decrease in ATP by NaF (1.5 mM) was dose-dependently inhibited by CV-2619 (0.3--30 microM). Inhibition of enolase and activation of PFK by NaF were still noted even in the presence of CV-2619. Inhibition of GAPDH by NaF, however, was released by CV-2619. Q-10 (1--100 microM) did not affect the ATP levels decreased by NaF. It could be concluded that CV-2619 counteracted the NaF-induced decrease in the ATP level by accelerating the glycolytic flux through the GAPDH step, which was a rate-limiting one in the presence of NaF. Q-10, however, had no effect on the glycolytic flux.
在有或无氟化钠(NaF)存在的情况下,研究了CV - 2619和泛醌 - 10(Q - 10)对斯普拉格 - 道利大鼠红细胞(RBC)能量代谢的影响。NaF(0.3 - 10 mM)剂量依赖性地降低了红细胞的三磷酸腺苷(ATP)和乳酸含量。在存在1.5 mM NaF的情况下,ATP含量降至对照的约30%。磷酸果糖激酶(PFK)被显著激活,而甘油醛 - 3 - 磷酸脱氢酶(GAPDH)和烯醇化酶则被NaF抑制。因此,NaF导致的ATP减少可能归因于后两种酶受抑制而使糖酵解受阻。1.5 mM NaF导致的ATP减少被CV - 2619(0.3 - 30 microM)剂量依赖性地抑制。即使存在CV - 2619,仍可观察到NaF对烯醇化酶的抑制和对PFK的激活。然而,CV - 2619可解除NaF对GAPDH的抑制。Q - 10(1 - 100 microM)对NaF降低的ATP水平没有影响。可以得出结论,CV - 2619通过加速糖酵解通量经GAPDH步骤(在存在NaF时这是一个限速步骤)来抵消NaF诱导的ATP水平降低。然而,Q - 10对糖酵解通量没有影响。