Hiltunen J K, Jauhonen V P, Savolainen M J, Hassinen I E
Biochem J. 1978 Feb 15;170(2):235-40. doi: 10.1042/bj1700235.
The metabolic effects of pent-4-enoate were studied in beating and potassium-arrested perfused rat hearts. The addition of 0.8mm-pent-4-enoate to the fluid used to perfuse a potassium-arrested heart resulted in a 70% increase in the O(2) consumption and a 66% decrease in the glycolytic flux as measured in terms of the de-tritiation of [3-(3)H]glucose, although the proportion of the O(2) consumption attributable to glucose oxidation decreased from an initial 30% to 10%. The pent-4-enoate-induced increase in O(2) consumption was only 15% in the beating heart. In the potassium-arrested heart, pent-4-enoate stimulated palmitate oxidation by more than 100% when measured in terms of the production of (14)CO(2) from [1-(14)C]palmitate, but in the beating heart palmitate oxidation was inhibited. Perfusion of the heart with pent-4-enoate had no effect on the proportion of pyruvate dehydrogenase found in the active form, in spite of large changes in the CoASH and acetyl-CoA concentrations and changes in their concentration ratios. The effects of pent-4-enoate on the cellular redox state were dependent on the ATP consumption of the heart. In the beating heart, pent-4-enoate caused a rapid mitochondrial NAD(+) reduction that subsequently faded out, so that the final state was more oxidized than the initial state. The arrested heart, however, remained in a more reduced state than initially, even after the partial re-oxidation that followed the initial rapid NAD(+) reduction. The ability of pent-4-enoate to increase or decrease fatty acid oxidation can be explained on the basis of the differential effects of pent-4-enoate on the concentration of citric acid-cycle intermediates under conditions of high or low ATP consumption of the myocardial cell. The proportion of the fatty acids in the fuel consumed by the heart is probably primarily determined by the regulatory mechanisms of glycolysis. When pent-4-enoate causes an increase in the citric acid-cycle intermediates, feedback inhibition of glycolysis results in an increase in the oxidation of fatty acids.
在搏动的和钾离子停搏的灌注大鼠心脏中研究了戊-4-烯酸酯的代谢效应。向用于灌注钾离子停搏心脏的液体中添加0.8mmol/L的戊-4-烯酸酯，导致氧耗增加70%，糖酵解通量降低66%（以[3-(3)H]葡萄糖的脱氚作用来衡量），尽管归因于葡萄糖氧化的氧耗比例从最初的30%降至10%。在搏动的心脏中，戊-4-烯酸酯引起的氧耗增加仅为15%。在钾离子停搏的心脏中，以[1-(14)C]棕榈酸酯产生(14)CO(2)来衡量，戊-4-烯酸酯刺激棕榈酸氧化超过100%，但在搏动的心脏中棕榈酸氧化受到抑制。用戊-4-烯酸酯灌注心脏对处于活性形式的丙酮酸脱氢酶的比例没有影响，尽管辅酶A和乙酰辅酶A的浓度以及它们的浓度比发生了很大变化。戊-4-烯酸酯对细胞氧化还原状态的影响取决于心脏的ATP消耗。在搏动的心脏中，戊-4-烯酸酯导致线粒体NAD(+)迅速还原，随后逐渐消失，因此最终状态比初始状态更氧化。然而，即使在初始快速NAD(+)还原后的部分再氧化之后，停搏的心脏仍比初始状态处于更还原的状态。戊-4-烯酸酯增加或减少脂肪酸氧化的能力可以基于戊-4-烯酸酯在心肌细胞ATP消耗高或低的条件下对柠檬酸循环中间产物浓度的不同影响来解释。心脏消耗的燃料中脂肪酸的比例可能主要由糖酵解的调节机制决定。当戊-4-烯酸酯导致柠檬酸循环中间产物增加时，糖酵解的反馈抑制导致脂肪酸氧化增加。
