Computer simulation of rat heart metabolism after adding glucose to the perfusate.

Computer simulation of rat heart metabolism after adding glucose to the perfusate.
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向灌注液中添加葡萄糖后大鼠心脏代谢的计算机模拟。

DOI:
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发表时间:
1977
影响因子:
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通讯作者:
D. Garfinkel
D. Garfinkel
中科院分区:
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文献类型:
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作者:
M. J. Achs;D. Garfinkel

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在没有底物的灌注大鼠心脏中突然给予灌注液中含有胰岛素的葡萄糖的实验中,用心脏能量代谢的计算机模型进行了模拟。线粒体代谢在细胞质控制下定量重组,脂肪酸氧化经历两步减少。克雷布斯循环(不同的反应以不同的速率进行)的不跨越主要是由于α -酮戊二酸脱氢酶的减慢;当细胞质葡萄糖达到一个新的稳定状态时,这个过程就结束了。已知体外线粒体的pH值高于其周围环境;我们在这里发现,这在原地也是成立的。在这些条件下,糖酵解是一致的底物控制,磷酸果糖激酶通常被认为是变构酶的典型例子。讨论了分析这类代谢数据的简单方法的局限性,例如,使用乳酸/丙酮酸比率来计算NADH/NAD比率。在这里,大量的酶和其他生化信息被整合到一个有生理意义的系统中。
An experiment where perfused rat hearts receiving no substrate are suddenly given glucose with insulin in the perfusate is simulated with a computer model of cardiac energy metabolism. Mitochondrial metabolism is quantitatively reorganized under cytoplasmic control, with fatty acid oxidation undergoing a two-step decrease. There is an unspanning of the Krebs cycle (different reactions going at different rates) due primarily to slowing of alpha-ketoglutarate dehydrogenase; this ends when cytoplasmic glucose reaches a new steady state. Mitochondria in vitro are known to have higher pH than their surroundings; it is found here that this also holds in situ. Under these conditions, glycolysis is coherently substrate controlled, as is phosphofructokinase, usually considered the typical example of an allosteric enzyme. Limitations on simple methods of analyzing metabolic data of this type, e.g., use of lactate/pyruvate ratios to calculate NADH/NAD ratios, are discussed. Here a large volume of enzyme and other biochemical information has been integrated into a physiologically meaningful system.