Interaction of mixed-function oxidation with biosynthetic processes. 1. Inhibition of gluconeogenesis by aminopyrine in perfused rat liver.
Interaction of mixed-function oxidation with biosynthetic processes. 1. Inhibition of gluconeogenesis by aminopyrine in perfused rat liver.
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混合功能氧化与生物合成过程的相互作用。
DOI：
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发表时间：
1973
期刊：
影响因子：
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通讯作者：
R. Thurman
中科院分区：
文献类型：
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作者：
R. Scholz;W. Hansen;R. Thurman
在空腹24小时、经苯巴比妥预处理的大鼠灌注的肝脏中，研究了乳酸糖异生。在乳酸浓度超过2 mM时，加入氨基比林（一种利用nadph的混合功能氧化的底物）后，乳酸的最大葡萄糖生成率被抑制到50%左右。氨基比林对二羟丙酮的次极大速率（即0.5-2 mM乳酸）或糖异生只有轻微影响，而在低糖异生速率下没有观察到抑制作用。数据与以下假设一致。在活跃的nadph利用过程中（如氨基吡啶的混合功能氧化），在糖异生途径中发生涉及苹果酸酶的无效循环，通过丙酮酸羧化酶反应增加通量来补偿。因此，当丙酮酸羧化酶达到最大活性时，糖异生受到抑制。假设观察到的糖异生抑制不是混合功能氧化所特有的，但可能是涉及线粒体外NADPH池的代谢相互依赖的更普遍机制的一个例子。
Gluconeogenesis from lactate was studied in perfused livers from phenobarbital-pretreated rats fasted for 24 h. Maximal rates of glucose production obtained with lactate concentrations of more than 2 mM were suppressed to about 50% following the addition of aminopyrine, a substrate for NADPH-utilizing mixed-function oxidations. Submaximal rates (i.e. with 0.5–2 mM lactate) or gluconeogenesis from dihydroxyacetone were only slightly affected by aminopyrine, whereas no inhibition was observed at low gluconeogenic rates. The data are consistent with the following hypothesis. In the presence of active NADPH-utilizing processes (such as mixed-function oxidation of aminopyrine) a futile cycle involving malic enzyme occurs in the pathway of gluconeogenesis which is compensated for by an increased flux through the pyruvate carboxylase reaction. Thus, gluconeogenesis is suppressed when maximal activity of pyruvate carboxylase is reached. It is assumed that the observed inhibition of gluconeogenesis is not specific for mixed-function oxidation, but may be an example for a more general mechanism of metabolic interdependences involving the extramitochondrial NADPH pool.