GLUTATHIONE-DEGRADING CAPACITIES OF LIVER AND KIDNEY IN DIFFERENT SPECIES

GLUTATHIONE-DEGRADING CAPACITIES OF LIVER AND KIDNEY IN DIFFERENT SPECIES
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DOI:
10.1016/0006-2952(90)90503-d
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发表时间:
1990-09-01
影响因子:
5.8
通讯作者:
BALLATORI, N
BALLATORI, N
中科院分区:
医学2区
文献类型:
--
作者:
HINCHMAN, CA;BALLATORI, N

文献摘要

被引文献

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虽然肝脏被认为是谷胱甘肽(GSH)合成的主要场所,但它被认为在GSH催化剂中仅起次要作用。这主要是因为在最常用的实验动物大鼠中,肝γ-谷氨酰转移酶(γ- GT)活性非常低,而肾活性相当高。γ- GT是唯一已知的催化GSH降解初始步骤的酶。本工作比较γ-六种哺乳动物肝脏、肾脏和胆囊中的GT和二肽酶活性,以评估相对于肾脏降解,GSH肝胆catenorization的重要性。在γ中观察到显著的物种差异。GT活性,以及两种γ-GT的肾与肝(K/L)比。GT浓度(毫单位/mg蛋白质)和整个器官活性(每个肝脏或两个肾脏的总活性)。γ-γ的K/L浓度比GT活性范围从大鼠的875到豚鼠的15。整个器官γ- GT比率为约1.0%。在小鼠和大鼠中为150,而在豚鼠、猪和猕猴中仅为2-5。从γ-γ-γ计算的人K/L比以前报道的GT活动与豚鼠相似。还观察到肽酶活性的K/L比的物种差异,尽管这些差异不如γ-K/L比的差异大。GT γ-还在所有检查物种的胆囊中测量了GT和二肽酶活性(不具有该器官的大鼠除外),发现与肝脏的活性相当。这些结果表明,在物种,如豚鼠,也许是人类,肝脏和胆道树发挥了突出的作用,谷胱甘肽营业额。因为肝脏的低γ和肾脏的高γ-大鼠的GT活性,并且因为它没有胆囊,该物种可能不是研究GSH和GSH缀合物的催化作用的最佳模型。在这些降解过程中,使用大鼠模型可能低估了肝脏的作用,而高估了肾脏的作用。
Although the liver is recognized as a major site of glutathione (GSH) synthesis, it is thought to play only a minor role in GSH catabolism. This is primarily because in the rat, the most commonly used experimental animal, hepatic .gamma.-glutamytransferase (.gamma.-GT) activity is very low, whereas kidney activity is quite high. .gamma.-GT is the only enzyme known to catalyze the initial step in GSH degradation. The present work compares .gamma.-GT and dipeptidase activities in liver, kidney, and gallbladder of six mammalian species to assess the importance of hepatobiliary catabolism of GSH, relative to renal degradation. Marked species differences were observed in .gamma.-GT activities, and in kidney to liver (K/L) ratios for both .gamma.-GT concentration (milliunits/mg protein) and whole organ activities (total activity per liver or two kidneys). The K/L concentration ratios for .gamma.-GT activities ranged from 875 in the rat to 15 in the guinea pig. Whole organ .gamma.-GT ratios were .apprx. 150 in mouse and rat, and only 2-5 in guinea pig, pig, and macaque. Human K/L ratios calculated from .gamma.-GT activities reported previously were similar to those of the guinea pig. Species differences were also observed in K/L ratios for peptidase activities, though these differences were not as large as those for .gamma.-GT. .gamma.-GT and dipeptidase activities were also measured in gallbladders of all species examined (except rat which does not have this organ), and were found to be comparable to those of liver. These results suggest that in species such as the guinea pig and perhaps humans, the liver and biliary tree play a prominent role in GSH turnover. Because of the low hepatic and high renal .gamma.-GT activities of the rat, and because it does not have a gallbladder, this species may not be the best model for studying the catabolism of GSH and GSH conjugates. Use of the rat model may underestimate the contribution of liver, and overestimate that of kidney, in these degradative processes.