HEPATIC GLUTATHIONE HOMEOSTASIS IN THE RAT - EFFLUX ACCOUNTS FOR GLUTATHIONE TURNOVER
HEPATIC GLUTATHIONE HOMEOSTASIS IN THE RAT - EFFLUX ACCOUNTS FOR GLUTATHIONE TURNOVER
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DOI：
10.1002/hep.1840040402
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发表时间：
1984-01-01
期刊：
影响因子：
13.5
通讯作者：
MITCHELL, JR
中科院分区：
文献类型：
--
作者：
LAUTERBURG, BH;ADAMS, JD;MITCHELL, JR
在雄性Sprague-Dawley大鼠体内测定了肝脏谷胱甘肽周转率以及谷胱甘肽从肝脏流出至胆汁和血液的量。在进食的大鼠中，从肝动静脉浓度梯度和肝血计算的谷胱甘肽流出到血液中的量为12.4 ±。1.4 nmol最小值g肝脏。连同谷胱甘肽排泄到胆汁中（3.4.+-. 0.4 nmol/min·cnt·dot. g肝脏）的总外排占谷胱甘肽的肝脏周转率为15.2 ± 0.5%。0.9 nmol/min·cnt·dot. g肝脏。禁食动物48小时显著增加肝脏谷胱甘肽周转率至26.4.+-。1.2 nmol/min·cnt·dot. g肝脏。增加外排到血液中，而不是增加肝内catalysts解释了这种增加的营业额。谷胱甘肽的全身清除率为3.22 ±。0.51 ml/min·cnt·dot. 100 g体重因此，根据谷胱甘肽的清除率和动脉浓度，计算出谷胱甘肽从肝脏的流出量占进入循环的总谷胱甘肽流入量的90%以上。因此，肝脏是血浆谷胱甘肽的主要来源，基础状态下肝脏谷胱甘肽的周转几乎完全由谷胱甘肽从肝脏的流出来解释。在禁食期间，外源性谷胱甘肽的血浆清除率增加至5.32 ± 0.001。0.35 ml/min·cnt·dot. 100 g体重时，谷胱甘肽合成对蛋氨酸的利用率显著提高。禁食期间肝外催化剂增加导致血浆谷胱甘肽减少，这反过来可能解释了观察到的肝谷胱甘肽周转率和合成率同时刺激的正弦谷胱甘肽外排增加。通过利用甲硫氨酸合成谷胱甘肽，肝脏因此能够在半胱氨酸的饮食来源不足时为其他器官提供更多的半胱氨酸。
Hepatic glutathione turnover and the efflux of glutathione from the liver into bile and blood were measured in male Sprague-Dawley rats in vivo. In fed rats the efflux of glutathione into blood, calculated from the hepatic arteriovenous concentration gradient and hepatic blood, amounted to 12.4 .+-. 1.4 nmol min .cntdot. g liver. Together with the excretion of glutathione into bile (3.4 .+-. 0.4 nmol/min .cntdot. g liver) total efflux accounted for the hepatic turnover of glutathione of 15.2 .+-. 0.9 nmol/min .cntdot. g liver. Fasting animals for 48 h markedly increased hepatic glutathione turnover to 26.4 .+-. 1.2 nmol/min .cntdot. g liver. Increased efflux into blood rather than increased intrahepatic catabolism accounted for this increased turnover. The systemic clearance of glutathione was 3.22 .+-. 0.51 ml/min .cntdot. 100 g body wt. The efflux of glutathione from liver therefore was calculated to contribute over 90% of total glutathione inflow into the circulation, as determined from the clearance and the arterial concentration of glutathione. Thus, the liver is the major source of plasma glutathione, and turnover of hepatic glutathione in the basal state is accounted for almost entirely by efflux of glutathione from the liver. During fasting, the plasma clearance of exogenous glutathione increased to 5.32 .+-. 0.35 ml/min .cntdot. 100 g body wt, and the utilization of methionine for glutathione synthesis increased markedly. The increased extrahepatic catabolism during fasting results in a decrease in plasma glutathione, which in turn may account for the observed increase in sinusoidal glutathione efflux with concomitant stimulation of the rate of hepatic glutathione turnover and of synthesis. By utilizing methionine for glutathione synthesis, the liver thus is able to make more cysteine available to other organs when dietary sources of cysteine are deficient.