Kobayashi K, Neely J R
J Mol Cell Cardiol. 1983 Jun;15(6):359-67. doi: 10.1016/0022-2828(83)90320-6.
The effects of myocardial ischemia and reperfusion on pyruvate dehydrogenase (PDH) activity were studied in isolated rat hearts. PDH remained largely (80%) in the active form during 10 min of whole heart ischemia in hearts receiving 11 mM glucose as substrate. With reperfusion, PDH was converted to the inactive form (45% by 2 min) and then returned slowly to control levels. Addition of pyruvate (10 mM) to the glucose containing perfusate during reperfusion prevent the reperfusion inactivation of PDH (96% active). The maintenance of a high percent of PDH in the active form during ischemia occurred in spite of high mitochondrial ratios of NADH/NAD and acetyl CoA/CoA and was related to a very low mitochondrial ATP/ADP ratio. The low ATP and high ADP would restrict PDH kinase phosphorylation and inactivation of PDH during ischemia. Reperfusion resulted in a rapid increase in mitochondrial ATP/ADP ratio and the increased availability of ATP as substrate for the kinase coupled with continued high levels of NADH and acetyl CoA which stimulate kinase activity may have accounted for the early inactivation of PDH with reperfusion. Addition of pyruvate to the perfusate probably inhibited the PDH kinase and prevent the reperfusion inactivation of PDH.
在离体大鼠心脏中研究了心肌缺血和再灌注对丙酮酸脱氢酶（PDH）活性的影响。以11 mM葡萄糖作为底物时，在全心缺血10分钟期间，PDH大部分（80%）保持活性形式。再灌注时，PDH转变为无活性形式（2分钟时为45%），然后缓慢恢复到对照水平。再灌注期间向含葡萄糖的灌注液中添加丙酮酸（10 mM）可防止PDH的再灌注失活（96%活性）。尽管线粒体中NADH/NAD和乙酰辅酶A/辅酶A的比例很高，但缺血期间仍有很高比例的PDH保持活性形式，这与线粒体中极低的ATP/ADP比例有关。低ATP和高ADP会限制缺血期间PDH激酶的磷酸化及PDH的失活。再灌注导致线粒体ATP/ADP比例迅速升高，ATP作为激酶底物的可用性增加，同时NADH和乙酰辅酶A水平持续升高，刺激激酶活性，这可能是再灌注时PDH早期失活的原因。向灌注液中添加丙酮酸可能抑制了PDH激酶并防止了PDH的再灌注失活。
