The metabolic role of branched-chain amino acids
The metabolic role of branched-chain amino acids
复制标题
DOI：
10.1016/s0899-9007(01)00740-7
复制
发表时间：
2002-03-01
期刊：
影响因子：
4.4
通讯作者：
Hanani, M
中科院分区：
文献类型：
--
作者：
Freund, HR;Hanani, M
肝脏被认为是氨基酸降解的主要部位。然而，骨骼肌是氨基酸代谢的另一个重要场所，因为它们分解代谢支链氨基酸（BCAA），这是独一无二的。除了作为非特异性碳源用于氧化作为肌肉的燃料外，它们还作为肌肉中蛋白质合成的前体。米勒和霍顿在大鼠中进行的实验2表明，亮氨酸、异亮氨酸和缬氨酸的大量氧化发生在肝外。Manchester在1965年发表的一篇开创性的短通讯中，对大鼠横膈膜将[14 C]氨基酸转化为14 CO2的能力进行了定量估计。曼彻斯特的研究结果表明，超过一半的[14 C]亮氨酸进入组织在隔膜中脱羧，相当大的比例甚至进一步降解。异亮氨酸（58%）和缬氨酸（31%）的脱羧百分比也很大。添加胰岛素引起亮氨酸氧化的小但一致的刺激。此外，出现在14 CO2的隔膜所采取的同位素的分数并没有明显下降，作为氨基酸的浓度上升，与同位素的量纳入蛋白质，这稳步下降，随着比活度下降。[3] 1972年，Odessey和Goldberg进一步深入研究了氧化可能是大鼠膈肌、比目鱼肌和趾长伸肌中亮氨酸（可能还有所有三种支链氨基酸）的主要代谢途径的可能性。4他们确定隔膜具有将亮氨酸J1- 14 C降解为14 CO2的显著能力。隔膜对亮氨酸的代谢依赖于浓度，亮氨酸的吸收和氧化随着外部浓度的增加而增加。此外，亮氨酸降解的量相对于其掺入蛋白质增加10倍，因为其外部浓度提高。红色比目鱼肌和苍白的伸趾长肌肌肉表现出类似的显着的亮氨酸氧化能力。这两种肌肉的CO2产生率、蛋白质合成率和总吸收率均低于膈肌。骨骼肌质量占身体质量的43%，是体内亮氨酸氧化的主要部位，标志着亮氨酸和其他支链氨基酸可能是肌肉的重要能量来源。肌肉中亮氨酸的完全氧化比葡萄糖的完全氧化产生更多的腺苷三磷酸分子（以摩尔计）。此外，肌肉氧化亮氨酸的这种固有能力在某些生理状态如食物匮乏下增加。5后来的工作确定，肌肉中支链氨基酸的氧化速率受代谢和激素调节。骨骼肌中的Buse和Reid 6以及心肌中的Chua等人7表明，亮氨酸还通过抑制蛋白质降解和增强蛋白质合成来调节肌细胞中蛋白质的周转。亮氨酸对肌肉蛋白质周转的调节影响了向负向的转变。
The liver is considered the major site of amino acid degradation. 1 However, skeletal muscles are another important site for amino acid metabolism because they catabolize branched-chain amino acids (BCAAs), which are unique. In addition to serving as a non-specific source of carbon for oxidation as fuel for the muscle, they serve as precursors for protein synthesis in the muscle. Experiments in the rat by Miller and Holden2 suggested that substantial oxidation of leucine, isoleucine, and valine takes place extrahepatically. Manchester, 3 in a pioneering short communication published in 1965, provided a quantitative estimate of the capacity of the rat diaphragm to convert [14C] amino acids into 14CO2. Manchester’s results showed that over half of the [14C] leucine entering the tissue is decarboxylated in the diaphragm and that a considerable proportion is degraded even further. The percentages of decarboxylation for isoleucine (58%) and valine (31%) also were substantial. Addition of insulin brought about a small but consistent stimulation of leucine oxidation. Moreover, the fraction of isotope taken up by the diaphragm appearing as 14CO2 did not decline markedly as the concentration of amino acids supplied rose, in contrast with the amount of isotope incorporated into protein, which dropped steadily as the specific activity fell. 3 Further extensive work exploring the possibility that oxidation might be a major metabolic pathway for leucine (and possibly all three BCAAs) in rat diaphragm and in soleus and extensor digitorm longus muscles was published in 1972 by Odessey and Goldberg. 4 They determined that the diaphragm posseses a marked ability to degrade leucine J1-14C to 14CO2. The metabolism of leucine by the diaphragm depended on the concentration, and leucine uptake and oxidation increased with increasing external concentrations. Further, the amount of leucine degradation relative to its incorporation into protein increased 10-fold as its external concentration was raised. The red soleus and pale extensor degitorum longus muscles exhibited a similar marked capacity for leucine oxidation. The rates of CO2 production, incorporation into protein, and total uptake in these two muscles were lower than those in the diaphragm.The skeletal muscle mass, which constitutes 43% of the body mass, is the major site for leucine oxidation in the body, marking leucine and possibly the other BCAAs as significant energy sources for the muscle. Complete oxidation of leucine in the muscle yields more adenosine triphosphate molecules on a molar basis than complete oxidation of glucose. Further, this inherent ability of muscle to oxidize leucine increases under certain physiologic states such as food deprivation. 5 Later work determined that the rate of oxidation of BCAA in muscle is under metabolic and hormonal regulation. Buse and Reid6 in skeletal muscle and Chua et al. 7 in cardiac muscle suggested that leucine also regulates the turnover of protein in muscle cells by inhibiting protein degradation and enhancing protein synthesis. This regulation of muscle protein turnover by leucine influences the transition to negative