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维生素A缺乏对大鼠肝脏、肾脏和肺中谷胱甘肽S-转移酶活性的影响。

The effect of vitamin A deficiency on hepatic, renal and pulmonary glutathione S-transferase activities in the rat.

作者信息

Siddik Z H, Mimnaugh E G, Trush M A, Gram T E

出版信息

Biochem J. 1980 Jun 15;188(3):889-93. doi: 10.1042/bj1880889.

DOI:10.1042/bj1880889
PMID:7470042
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1161974/
Abstract

Feeding male weanling rats on a vitamin A-deficient diet for 6 weeks resulted in significant increases (44-57%) in glutathione S-aryl-, S-aralkyl- S-alkyl- and S-epoxidetransferase activities in the liver cytosol. Only the S-aralkyl- (27%) and S-alkyltransferase (14%) activities were significantly increased in the kidney as a result of deficiency. There was no effect on any of the pulmonary glutathione S-transferase activities. The increases in hepatic transferase activities were due primarily to increases (25-96%) in the apparent Vmax. There were no changes in the apparant Km of any of the four drug substrates employed. With 3,4-dichloronitrobenzene as the second substrate, the apparent Km for glutathione was increased by over 2-fold in vitamin A-deficient livers as compared with controls. The relationship between these results and enhanced susceptibility to chemical carcinogens in vitamin A deficiency is briefly discussed, and comparison is made between the effects of this nutritional state and pretreatment with drug inducers on the glutathione S-transferases.

摘要

给雄性断奶大鼠喂食缺乏维生素A的饲料6周,导致肝细胞质中谷胱甘肽S-芳基、S-芳烷基、S-烷基和S-环氧化物转移酶活性显著增加(44%-57%)。由于缺乏维生素A,肾脏中只有S-芳烷基转移酶(27%)和S-烷基转移酶(14%)的活性显著增加。对任何肺谷胱甘肽S-转移酶活性均无影响。肝转移酶活性的增加主要是由于表观Vmax增加(25%-96%)。所使用的四种药物底物的表观Km均无变化。以3,4-二氯硝基苯作为第二种底物,与对照组相比,维生素A缺乏的肝脏中谷胱甘肽的表观Km增加了2倍以上。简要讨论了这些结果与维生素A缺乏时对化学致癌物易感性增加之间的关系,并比较了这种营养状态和药物诱导剂预处理对谷胱甘肽S-转移酶的影响。

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本文引用的文献

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Studies on glutathione S-alkyltransferase of the rat.大鼠谷胱甘肽S-烷基转移酶的研究。
Biochem J. 1966 Jan;98(1):44-56. doi: 10.1042/bj0980044.
2
Conjugations with glutathione. Distribution of glutathione S-aryltransferase in vertebrate species.与谷胱甘肽的结合。谷胱甘肽S-芳基转移酶在脊椎动物物种中的分布。
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Vitamin A deficiency enhances binding of benzo(a)pyrene to tracheal epithelial DNA.维生素A缺乏会增强苯并(a)芘与气管上皮DNA的结合。
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Enzymatic conjugation of epoxides with glutathione.环氧化物与谷胱甘肽的酶促共轭反应。
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Glutathione S-transferases. The first enzymatic step in mercapturic acid formation.谷胱甘肽S-转移酶。硫醚氨酸形成过程中的首个酶促步骤。
J Biol Chem. 1974 Nov 25;249(22):7130-9.
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Vitamin A status and hepatic drug metabolism in the rat.大鼠体内维生素A状态与肝脏药物代谢
Can J Physiol Pharmacol. 1973 Jan;51(1):6-11. doi: 10.1139/y73-002.
7
On the functional site of vitamin A.关于维生素A的功能位点。
J Vitaminol (Kyoto). 1969 Sep 10;15(3):254-60. doi: 10.5925/jnsv1954.15.254.
8
Hepatic drug metabolism in retinol-deficient rats.维生素A缺乏大鼠的肝脏药物代谢
Biochem Pharmacol. 1975 Sep 1;24(17):1645-6. doi: 10.1016/0006-2952(75)90096-9.
9
Drug induction and sex differences of renal glutathione S-transferases in the rat.大鼠肾谷胱甘肽S-转移酶的药物诱导及性别差异
Biochem J. 1975 Aug;150(2):259-62. doi: 10.1042/bj1500259.
10
Ligandin, the glutathione S-transferases, and chemically induced hepatocarcinogenesis: a review.配体蛋白、谷胱甘肽S-转移酶与化学诱导的肝癌发生:综述
Cancer Res. 1977 Jan;37(1):8-14.