Sendelbach L E, White C A, Howell S, Gregus Z, Klaassen C D
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City 66103.
Toxicol Appl Pharmacol. 1990 Feb;102(2):259-67. doi: 10.1016/0041-008x(90)90025-p.
Low dietary concentrations of methionine and cysteine are known to decrease hepatic glutathione content. However, it is not known if restricting the dietary content of these sulfur containing amino acids also affects hepatic levels of adenosine 3'-phosphate 5'-phosphosulfate (PAPS), the cofactor for sulfation, or metallothionein, a protein rich in sulfhydryl groups. Rats were fed diets lacking cysteine and containing various concentrations of methionine (0.15, 0.3, or 0.6%) for 8 days. Control diet contained 0.3% each of methionine and cysteine. Hepatic glutathione levels were decreased approximately 75% in rats fed diets containing 0.15 or 0.3% methionine. In contrast, PAPS and hepatic metallothionein concentrations were not decreased by the low sulfhydryl diets. Additionally, rats on the various diets were challenged by the administration of ZnCl2 (3 mmol/kg. sc). In both control rats and rats maintained on sulfhydryl-deficient diets, ZnCl2 increased hepatic metallothionein to the same level. However, significantly lower levels of PAPS were observed after ZnCl2 in rats receiving sulfhydryl-deficient diets than in controls. In summary, restriction of dietary sulfhydryl markedly decreases the hepatic content of glutathione and has a minor effect on PAPS concentration, but does not decrease the basal hepatic concentration of metallothionein or its induction by ZnCl2.
已知饮食中甲硫氨酸和半胱氨酸浓度较低会降低肝脏中的谷胱甘肽含量。然而,尚不清楚限制这些含硫氨基酸的饮食含量是否也会影响硫酸化辅因子3'-磷酸5'-磷酸腺苷硫酸酯(PAPS)的肝脏水平,或金属硫蛋白(一种富含巯基的蛋白质)的肝脏水平。给大鼠喂食缺乏半胱氨酸且含有不同浓度甲硫氨酸(0.15%、0.3%或0.6%)的饲料,持续8天。对照饲料中甲硫氨酸和半胱氨酸各含0.3%。喂食含0.15%或0.3%甲硫氨酸饲料的大鼠肝脏谷胱甘肽水平降低了约75%。相比之下,低巯基饮食并未降低PAPS和肝脏金属硫蛋白的浓度。此外,给不同饮食组的大鼠注射ZnCl2(3 mmol/kg,皮下注射)进行刺激。在对照大鼠和维持低巯基饮食的大鼠中,ZnCl2均使肝脏金属硫蛋白增加到相同水平。然而,接受低巯基饮食的大鼠在注射ZnCl2后观察到的PAPS水平显著低于对照组。总之,限制饮食中的巯基会显著降低肝脏中的谷胱甘肽含量,对PAPS浓度有轻微影响,但不会降低肝脏中金属硫蛋白的基础浓度或其对ZnCl2的诱导反应。