1. Radioactively labelled 4-methyl-2-oxopentanoate was taken up by isolated pancreatic islets in a concentration- and pH-dependent manner and led to the intracellular accumulation of labelled amino acid and to a decrease in the intracellular pH. Uptake of 4-methyl-2-oxopentanoate did not appear to be either electrogenic or Na+-dependent. The islet content of 2-oxo acid radioactivity was not affected by either 2-cyano-3-hydroxy-cinnamate (10mM) or pyruvate (10mM), although both these substances inhibited the oxidation of [U-14C]4-methyl-2-oxopentanoate by islet tissue. 2. 4-Methyl-2-oxopentanoate markedly stimulated islet-cell respiration, ketone-body formation and biosynthetic activity. The metabolism of endogenous nutrients by islets appeared to be little affected by the compound. 3. Studies with the 3H- and 14C-labelled substrate revealed that 4-methyl-2-oxopentanoate was incorporated by islets into CO2, water, acetoacetate, L-leucine and to a lesser extent into islet protein and lipid. Carbon atoms C-2, C-3 and C-4 of the acetoacetate produced were derived from the carbon skeleton of the 4-methyl-2-oxopentanoate, but the acetoacetate carboxy group was derived from the incorporation of CO2. These results, and consideration of the relative rates of 14CO2 and acetoacetate formation from 1-14C-labelled as opposed to U-14C-labelled 4-methyl-2-oxopentanoate, led to the conclusion that the pathway of catabolism of this 2-oxo acid in pancreatic islets is identical with that described in other tissues. The amination of 4-methyl-2-oxopentanoate by islets was attributed to the presence of a branched-chain amino acid aminotransferase (EC 2.6.1.42) activity in the tissue. Although glutamate dehydrogenase activity was demonstrated in islet tissue, the reductive amination of 2-oxoacids did not seem to be of importance in the formation of leucine from 4-methyl-2-oxopentanoate. 4. The results of experiments with respiratory inhibitors and uncouplers, and the finding that 14CO2 production and islet respiration were linked in a 1:1 stoicheiometry suggested that 4-methyl-2-oxopentanoate catabolism was coupled to mitochondrial oxidative phosphorylation. The catabolism of 4-methyl-2-oxopentanoate in islet tissue appeared to be regulated at the level of the initial 2-oxo acid dehydrogenase (EC 1.2.1.25) reaction.

中文翻译：

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大鼠胰岛中4-甲基-2-氧戊酸的代谢。

1.放射性标记的4-甲基-2-氧戊酸被分离的胰岛以浓度和pH依赖的方式吸收，并导致标记氨基酸在细胞内积累，并降低细胞内pH。4-甲基-2-氧戊酸的摄取似乎不是电性的或Na +依赖性的。2-氧代酸放射性的胰岛含量不受2-氰基-3-羟基肉桂酸酯（10mM）或丙酮酸（10mM）的影响，尽管这两种物质均抑制[U-14C] 4-甲基-2的氧化-氧戊酸通过胰岛组织。2. 2-氧2-戊酸4-甲酯能明显刺激胰岛细胞的呼吸，酮体的形成和生物合成活性。胰岛对内源性营养物质的代谢似乎几乎不受该化合物的影响。3。用3H和14C标记的底物进行的研究表明，4-甲基-2-氧戊酸通过胰岛引入二氧化碳，水，乙酰乙酸酯，L-亮氨酸中，并在较小程度上引入胰岛蛋白质和脂质中。产生的乙酰乙酸酯的碳原子C-2，C-3和C-4衍生自4-甲基-2-氧戊酸的碳骨架，而乙酰乙酸酯的羧基衍生自CO2的引入。这些结果，以及从1-14C标记的U-14C标记的4-甲基-2-氧戊酸的14CO2和乙酰乙酸形成的相对速率的考虑，得出以下结论：该2-氧代的分解代谢途径胰岛中的酸与其他组织中描述的酸相同。胰岛中的4-甲基-2-氧代戊酸酯的胺化归因于组织中存在支链氨基酸氨基转移酶（EC 2.6.1.42）活性。尽管在胰岛组织中证实了谷氨酸脱氢酶的活性，但是2-氧代酸的还原胺化在由4-甲基-2-氧代戊酸形成亮氨酸中似乎并不重要。4.呼吸抑制剂和解偶联剂的实验结果以及以14：1的化学计量关系发现14CO2的产生和胰岛呼吸有关的发现表明4-甲基-2-氧戊酸酯代谢与线粒体氧化磷酸化有关。胰岛组织中的4-甲基-2-氧代戊酸酸酯的分解代谢似乎在初始的2-氧代酸脱氢酶（EC 1.2.1.25）反应的水平受到调节。尽管在胰岛组织中证实了谷氨酸脱氢酶的活性，但是2-氧代酸的还原胺化在由4-甲基-2-氧代戊酸形成亮氨酸中似乎并不重要。4.呼吸抑制剂和解偶联剂的实验结果以及以14：1的化学计量关系发现14CO2的产生和胰岛呼吸有关的发现表明4-甲基-2-氧戊酸酯代谢与线粒体氧化磷酸化有关。胰岛组织中的4-甲基-2-氧代戊酸酸酯的分解代谢似乎在初始的2-氧代酸脱氢酶（EC 1.2.1.25）反应的水平受到调节。尽管在胰岛组织中证实了谷氨酸脱氢酶的活性，但是2-氧代酸的还原胺化在由4-甲基-2-氧代戊酸形成亮氨酸中似乎并不重要。4.呼吸抑制剂和解偶联剂的实验结果以及以14：1的化学计量关系发现14CO2产生和胰岛呼吸有关的发现表明，4-甲基-2-氧戊酸酯代谢与线粒体氧化磷酸化有关。胰岛组织中的4-甲基-2-氧代戊酸酸酯的分解代谢似乎在初始的2-氧代酸脱氢酶（EC 1.2.1.25）反应的水平受到调节。呼吸抑制剂和解偶联剂的实验结果，以及14CO2的产生和胰岛呼吸作用以1：1的化学计量关系联系在一起的发现，表明4-甲基-2-氧opentanoate分解代谢与线粒体氧化磷酸化有关。胰岛组织中的4-甲基-2-氧代戊酸酸酯的分解代谢似乎在初始的2-氧代酸脱氢酶（EC 1.2.1.25）反应的水平受到调节。呼吸抑制剂和解偶联剂的实验结果，以及14CO2的产生和胰岛呼吸作用以1：1的化学计量关系联系在一起的发现，表明4-甲基-2-氧opentanoate分解代谢与线粒体氧化磷酸化有关。胰岛组织中的4-甲基-2-氧代戊酸酸酯的分解代谢似乎在初始的2-氧代酸脱氢酶（EC 1.2.1.25）反应的水平受到调节。