Regina M, Korhonen V P, Smith T K, Alakuijala L, Eloranta T O
Department of Biochemistry and Biotechnology, University of Kuopio, Finland.
Arch Biochem Biophys. 1993 Feb 1;300(2):598-607. doi: 10.1006/abbi.1993.1083.
Rats were fed toxic levels of methionine with or without simultaneous dietary supplements of glycine and serine. Feed intake, growth rate, and metabolite concentrations in intestine, plasma, liver, skeletal muscle, and kidneys were monitored. Both toxic amounts of methionine and supplemental glycine and serine affected the tissue distribution of several amino acids resulting in similar, opposite, and diet-specific effects on the parameters studied. These changes were considered to be normal responses of amino acid metabolism to diet and to reflect metabolite flows between tissues. The feeding of toxic levels of methionine resulted in the accumulation of methionine, taurine, and glutathione in all tissues measured, but caused marked accumulation of S-adenosylmethionine and its catabolites only in liver. Hepatic accumulation of S-adenosylmethionine was accompanied by 40% stimulation of methionine adenosyltransferase and 40% repression of spermine synthase over a 2-week period. Simultaneous dietary supplements of glycine and serine combined with toxic levels of methionine markedly stimulated hepatic methionine catabolism. As a result, tissue distribution of methionine and glutathione returned close to normal in all tissues measured and accumulation of hepatic S-adenosylmethionine and its catabolites was prevented. Concentrations of taurine in liver, blood, and kidneys were further elevated, suggesting increased conversion of methionine to taurine followed by urinary excretion. These changes were accompanied by normalization of the above enzyme activities and the absence of symptoms of methionine toxicity. It was concluded that methionine toxicity is likely to be linked to hepatic accumulation of S-adenosylmethionine, resulting in liver dysfunction probably due to nonenzymatic methylation of liver macromolecules. Accumulation of tissue glutathione may also contribute to toxicity.
给大鼠喂食有毒剂量的蛋氨酸，同时给予或不给予甘氨酸和丝氨酸的膳食补充剂。监测大鼠的采食量、生长速率以及肠道、血浆、肝脏、骨骼肌和肾脏中的代谢物浓度。有毒剂量的蛋氨酸以及补充的甘氨酸和丝氨酸均会影响几种氨基酸的组织分布，从而对所研究的参数产生相似、相反以及特定于饮食的影响。这些变化被认为是氨基酸代谢对饮食的正常反应，并反映了组织间的代谢物流。喂食有毒剂量的蛋氨酸会导致所测所有组织中蛋氨酸、牛磺酸和谷胱甘肽的积累，但仅在肝脏中导致S-腺苷甲硫氨酸及其分解代谢产物的显著积累。在两周的时间里，肝脏中S-腺苷甲硫氨酸的积累伴随着蛋氨酸腺苷转移酶40%的刺激和精胺合酶40%的抑制。同时给予甘氨酸和丝氨酸的膳食补充剂并结合有毒剂量的蛋氨酸，可显著刺激肝脏中的蛋氨酸分解代谢。结果，所测所有组织中蛋氨酸和谷胱甘肽的组织分布恢复接近正常，并且肝脏中S-腺苷甲硫氨酸及其分解代谢产物的积累得到了预防。肝脏、血液和肾脏中的牛磺酸浓度进一步升高，表明蛋氨酸向牛磺酸的转化增加，随后经尿液排泄。这些变化伴随着上述酶活性的正常化以及蛋氨酸毒性症状的消失。得出的结论是，蛋氨酸毒性可能与肝脏中S-腺苷甲硫氨酸的积累有关，这可能导致肝脏功能障碍，可能是由于肝脏大分子的非酶甲基化。组织谷胱甘肽的积累也可能导致毒性。
