Wessels Anna G, Kluge Holger, Hirche Frank, Kiowski Andreas, Schutkowski Alexandra, Corrent Etienne, Bartelt Jörg, König Bettina, Stangl Gabriele I
Institute of Agricultural and Nutritional Sciences, Martin Luther University Halle-Wittenberg, 06120, Halle (Saale), Germany.
AJINOMOTO EUROLYSINE S.A.S., 75817, Paris Cedex 17, France.
PLoS One. 2016 Mar 1;11(3):e0150376. doi: 10.1371/journal.pone.0150376. eCollection 2016.
In addition to its role as an essential protein component, leucine (Leu) displays several other metabolic functions such as activation of protein synthesis. This property makes it an interesting amino acid for the therapy of human muscle atrophy and for livestock production. However, Leu can stimulate its own degradation via the branched-chain keto acid dehydrogenase complex (BCKDH). To examine the response of several tissues to excessive Leu, pigs were fed diets containing two- (L2) and four-fold (L4) higher Leu contents than the recommended amount (control). We found that the L4 diet led to a pronounced increase in BCKDH activity in the brain (2.5-fold, P < 0.05), liver (1.8-fold, P < 0.05) and cardiac muscle (1.7-fold, P < 0.05), whereas we found no changes in enzyme activity in the pancreas, skeletal muscle, adipose tissue and intestinal mucosa. The L2 diet had only weak effects on BCKDH activity. Both high Leu diets reduced the concentrations of free valine and isoleucine in nearly all tissues. In the brain, high Leu diets modified the amount of tryptophan available: for serotonin synthesis. Compared to the controls, pigs treated with the high Leu diets consumed less food, showed increased plasma concentrations of 3-hydroxybutyrate and reduced levels of circulating serotonin. In conclusion, excessive Leu can stimulate BCKDH activity in several tissues, including the brain. Changes in cerebral tryptophan, along with the changes in amino acid-derived metabolites in the plasma may limit the use of high Leu diets to treat muscle atrophy or to increase muscle growth.
除了作为一种必需的蛋白质成分发挥作用外，亮氨酸（Leu）还具有其他几种代谢功能，如激活蛋白质合成。这一特性使其成为治疗人类肌肉萎缩和用于畜牧生产的一种有趣的氨基酸。然而，亮氨酸可通过支链酮酸脱氢酶复合体（BCKDH）刺激自身降解。为了研究几种组织对过量亮氨酸的反应，给猪喂食亮氨酸含量比推荐量（对照）高两倍（L2）和四倍（L4）的日粮。我们发现，L4日粮导致脑（2.5倍，P<0.05）、肝脏（1.8倍，P<0.05）和心肌（1.7倍，P<0.05）中BCKDH活性显著增加，而我们发现胰腺、骨骼肌、脂肪组织和肠黏膜中的酶活性没有变化。L2日粮对BCKDH活性只有微弱影响。两种高亮氨酸日粮几乎降低了所有组织中游离缬氨酸和异亮氨酸的浓度。在脑中，高亮氨酸日粮改变了可用于5-羟色胺合成的色氨酸量。与对照组相比，用高亮氨酸日粮处理的猪食物摄入量减少，血浆3-羟基丁酸浓度升高，循环5-羟色胺水平降低。总之，过量亮氨酸可刺激包括脑在内的几种组织中的BCKDH活性。脑色氨酸的变化以及血浆中氨基酸衍生代谢物的变化可能会限制使用高亮氨酸日粮治疗肌肉萎缩或促进肌肉生长。
