Holecek M, Sprongl L, Tichý M, Pecka M
Department of Physiology, Charles University School of Medicine, Hradec Králové, Czech Republic.
Metabolism. 1998 Jun;47(6):681-5. doi: 10.1016/s0026-0495(98)90030-0.
To evaluate the contribution of hepatic tissue to alterations in the metabolism of proteins and the branched-chain amino acids (BCAA) leucine, isoleucine, and valine in systemic inflammatory response syndrome, we studied the changes of leucine metabolism in isolated perfused liver (IPL) of endotoxin-treated rats. Male albino rats were injected with the endotoxin of Salmonella enteritidis (5 mg x kg(-1)) or saline (control). Four hours later, leucine and ketoisocaproate (KIC) oxidation and incorporation into liver proteins were determined in IPL using the single-pass liver perfusion technique. L-[1-(14)C]leucine and alpha-keto[1-(14)C]isocaproic acid were used as a tracer in two separate experiments. Endotoxin treatment resulted in a decrease of plasma BCAA levels, an increase of leucine oxidation, and a decrease of KIC oxidation by IPL. Leucine incorporation into liver proteins was lower in endotoxin-treated rats, and we did not find measurable incorporation of the labeled carbon of KIC in liver proteins in either group of animals. The sum of individual amino acid concentrations in the effluent perfusate was higher in endotoxin-treated animals, although only leucine and phenylalanine increased significantly. The decrease in KIC oxidation indicates a decreased capacity of hepatic tissue to oxidize branched-chain ketoacids (BCKA). The increase in leucine oxidation by IPL of endotoxin-treated rats indicates an increase in BCAA aminotransferase activity. These changes demonstrate an important response of the body that enables the resynthesis of essential BCAA from their ketoanalogs delivered to the liver from peripheral tissues, particularly muscle.
为评估肝组织在全身炎症反应综合征中对蛋白质及支链氨基酸（亮氨酸、异亮氨酸和缬氨酸）代谢改变的作用，我们研究了内毒素处理大鼠的离体灌注肝（IPL）中亮氨酸代谢的变化。雄性白化大鼠注射肠炎沙门氏菌内毒素（5 mg·kg⁻¹）或生理盐水（对照）。4小时后，采用单通道肝脏灌注技术测定IPL中亮氨酸和酮异己酸（KIC）的氧化及掺入肝蛋白的情况。在两个独立实验中分别使用L-[1-(¹⁴)C]亮氨酸和α-酮[1-(¹⁴)C]异己酸作为示踪剂。内毒素处理导致血浆支链氨基酸水平降低、亮氨酸氧化增加以及IPL中KIC氧化减少。内毒素处理大鼠中亮氨酸掺入肝蛋白的量较低，并且在两组动物中均未发现KIC标记碳在肝蛋白中的可测量掺入。内毒素处理动物的流出灌注液中单个氨基酸浓度之和较高，尽管只有亮氨酸和苯丙氨酸显著增加。KIC氧化的减少表明肝组织氧化支链酮酸（BCKA）的能力下降。内毒素处理大鼠的IPL中亮氨酸氧化增加表明支链氨基酸转氨酶活性增加。这些变化表明身体的一种重要反应，即能够从外周组织（特别是肌肉）输送到肝脏的酮类似物重新合成必需的支链氨基酸。
