Higgins T J, Bailey P J
Biochim Biophys Acta. 1983 Feb 16;762(1):67-75. doi: 10.1016/0167-4889(83)90118-0.
Isolated rat hearts perfused in the presence of iodoacetate show inhibition of glycolysis and release enzymes into the perfusate. Hearts perfused with cyanide, a mitochondrial inhibitor, show acceleration of glycolysis and no enzyme release. The adenine nucleotide content of the iodoacetate, but not the cyanide-perfused hearts was reduced. These results indicate that the membranes were permeable in the former treatment group. The adenylate energy charge and the ATP content of both the cyanide and iodoacetate treatment groups were similar but, as the extent of enzyme release was quite different, it appears that the energy state of the cell was not the prime factor controlling membrane integrity. Isolated perfused hearts were rendered ischaemic by placing a one-way ball valve in the aortic outflow tract. ATP concentration declined, as did ADP after an initial rise of short duration. AMP concentrations rose as the time of ischaemia increased. At the time at which enzyme release was first determined, the intracellular total adenine nucleotide content began to decline, suggesting that the membrane had become permeable to both small and large molecules. Glycolysis was stimulated by the hypoxia induced in the preparation and then this increase became inhibited. The point at which this inhibition was observed was also the point at which membrane permeability was evident. Taken together, the data from these experiments suggest that the energy derived from the activity of the glycolytic pathway may be important to the heart for maintenance of membrane function, particularly in ischaemia.
在碘乙酸存在的情况下灌注的离体大鼠心脏表现出糖酵解受到抑制且有酶释放到灌注液中。用线粒体抑制剂氰化物灌注的心脏则表现出糖酵解加速且无酶释放。碘乙酸灌注的心脏的腺嘌呤核苷酸含量降低，而氰化物灌注的心脏则没有。这些结果表明在前一个治疗组中细胞膜是可渗透的。氰化物和碘乙酸治疗组的腺苷酸能量电荷和ATP含量相似，但由于酶释放的程度差异很大，似乎细胞的能量状态不是控制膜完整性的主要因素。通过在主动脉流出道放置一个单向球阀使离体灌注心脏缺血。ATP浓度下降，ADP在短暂的初始升高后也下降。随着缺血时间的增加，AMP浓度升高。在首次测定酶释放时，细胞内总腺嘌呤核苷酸含量开始下降，这表明细胞膜对小分子和大分子都变得可渗透了。制备过程中诱导的缺氧刺激了糖酵解，随后这种增加受到抑制。观察到这种抑制的时间点也是膜通透性明显的时间点。综合来看，这些实验的数据表明糖酵解途径活动产生的能量对心脏维持膜功能可能很重要，尤其是在缺血情况下。
