Regulation of energy metabolism of the heart during acute increase in heart work
Regulation of energy metabolism of the heart during acute increase in heart work
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DOI：
10.1074/jbc.273.45.29530
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发表时间：
1998-11-06
影响因子：
4.8
通讯作者：
Taegtmeyer, H
中科院分区：
文献类型：
--
作者：
Goodwin, GW;Taylor, CS;Taegtmeyer, H
我们使用具有收缩性能和耗氧量生理值的离体工作大鼠心脏，测定了在心脏工作急性增加（1 μ M肾上腺素，后负荷增加40%）期间所有主要能量底物（葡萄糖、糖原、乳酸、油酸和甘油三酯）的贡献和关键调节酶的参与。我们根据底物的氧化速率定量地计算了氧气消耗，以每分钟为单位进行测量。总β -氧化（但不是外源性油酸氧化）随着功的跳跃而增加，与丙二酰辅酶a水平的降低一致。糖原和乳酸盐是心脏功急剧增加时碳底物的重要缓冲物。糖原导致高呼吸的机制有三：1)碳水化合物氧化选择性增加；2)葡萄糖氧化刺激延迟葡萄糖摄取；3)糖原衍生的丙酮酸与细胞外葡萄糖衍生的丙酮酸表现不同。尽管与磷酸化酶相比，丙酮酸脱氢酶的激活延迟，糖原衍生的丙酮酸与氧化的耦合更紧密。此外，糖原衍生的乳酸和丙酮酸有助于乳酸相对于丙酮酸的相对外排增加，从而调节氧化还原。糖原合成是由糖原合成酶的激活引起的，但由于磷酸化酶a被高细胞内葡萄糖抑制，因此选择了时间来最小化无效循环。
We determined the contribution of all major energy substrates (glucose, glycogen, lactate, oleate, and triglycerides) during an acute increase in heart work (1 mu M epinephrine, afterload increased by 40%) and the involvement of key regulatory enzymes, using isolated working rat hearts exhibiting physiologic values for contractile performance and oxygen consumption. We accounted for oxygen consumption quantitatively from the rates of substrate oxidation, measured on a minute-to-minute basis. Total beta-oxidation (but not exogenous oleate oxidation) was increased by the work jump, consistent with a decrease in the level of malonyl-CoA. Glycogen and lactate were important buffers for carbon substrate when heart work was acutely increased. Three mechanisms contributed to high respiration from glycogen: 1) carbohydrate oxidation was increased selectively; 2) stimulation of glucose oxidation was delayed at glucose uptake; and 3) glycogen-derived pyruvate behaved differently from pyruvate derived from extracellular glucose. Despite delayed activation of pyruvate dehydrogenase relative to phosphorylase, glycogen-derived pyruvate was more tightly coupled to oxidation. Also, glycogen-derived lactate plus pyruvate contributed to an increase in the relative efflux of lactate versus pyruvate, thereby regulating the redox. Glycogen synthesis resulted from activation of glycogen synthase late in the protocol but was timed to minimize futile cycling, since phosphorylase a became inhibited by high intracellular glucose.