Holecek M, Sprongl L, Skopec F, Andrýs C, Pecka M
Department of Physiology, Charles University School of Medicine, Hradec Králové, Czech Republic.
Am J Physiol. 1997 Dec;273(6):E1052-8. doi: 10.1152/ajpendo.1997.273.6.E1052.
The effects of tumor necrosis factor-alpha (TNF-alpha; cachectin) and lipopolysaccharide of Salmonella enteritidis (LPS; endotoxin) on leucine metabolism in rats were evaluated in the whole body using intravenous infusion of L-[1-14C]leucine and in isolated perfused liver (IPL) using the single-pass perfusion technique with alpha-keto[1-14C]isocaproate as a tracer for measurement of ketoisocaproic acid (KIC) oxidation, and the recirculation technique for measurement of hepatic amino acid exchanges. The data obtained in TNF-alpha and LPS groups were compared with those obtained in controls. Both TNF-alpha and LPS treatment induced an increase of whole body leucine turnover, oxidation, and clearance. As the result of a higher increase of leucine oxidation than of incorporation into the pool of body proteins, the fractional oxidation of leucine was increased. The fractional rate of protein synthesis increased significantly in the spleen (both in TNF-alpha and LPS rats), in blood plasma, liver, colon, kidneys, gastrocnemius muscle (in LPS rats), and in lungs (TNF-alpha-treated rats), whereas it decreased in the jejunum (LPS rats). In IPL of TNF-alpha- and LPS-treated rats a decrease of KIC oxidation and higher uptake of branched-chain amino acids (BCAA; valine, leucine, and isoleucine) were observed when compared with control animals. We hypothesize that the negative consequences of increased whole body proteolysis and of increased oxidation of BCAA induced by TNF-alpha and/or LPS are reduced by decreased activity of hepatic branched-chain ketoacid dehydrogenase that can help resupply BCAA to the body.
通过静脉输注L-[1-14C]亮氨酸在整体动物水平评估肿瘤坏死因子-α（TNF-α；恶病质素）和肠炎沙门氏菌脂多糖（LPS；内毒素）对大鼠亮氨酸代谢的影响，同时在离体灌注肝脏（IPL）中，采用单程灌注技术，以α-酮[1-14C]异己酸作为示踪剂测量酮异己酸（KIC）氧化，并采用再循环技术测量肝脏氨基酸交换。将TNF-α组和LPS组获得的数据与对照组的数据进行比较。TNF-α和LPS处理均导致整体亮氨酸周转率、氧化率和清除率增加。由于亮氨酸氧化增加幅度高于其掺入机体蛋白质池的幅度，亮氨酸的氧化分数增加。蛋白质合成分数率在脾脏（TNF-α组和LPS组大鼠）、血浆、肝脏、结肠、肾脏、腓肠肌（LPS组大鼠）和肺（TNF-α处理组大鼠）中显著增加，而在空肠（LPS组大鼠）中降低。与对照动物相比，在TNF-α和LPS处理的大鼠的IPL中，观察到KIC氧化减少以及支链氨基酸（BCAA；缬氨酸、亮氨酸和异亮氨酸）摄取增加。我们推测，TNF-α和/或LPS诱导的全身蛋白水解增加和BCAA氧化增加的负面后果，可通过肝脏支链酮酸脱氢酶活性降低得到缓解，这有助于为机体重新补充BCAA。
