的贡献酶α,gamma-elimination反应的解毒途径在小鼠肝脏硒代蛋氨酸。

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黑田Okuno T,日本久保田公司T, T,上野H, Nakamuro K

的贡献酶α,gamma-elimination反应的解毒途径在小鼠肝脏硒代蛋氨酸。

Toxicol:杂志。2001年10月1日,176 (1):18 - 23。

PubMed ID

11578145 (在PubMed

]

文摘

本研究的目的是阐明硒代蛋氨酸的解毒途径(SeMet)在小鼠肝脏。已经假定SeMet可能对硒代半胱氨酸代谢(SeCyH)通过途径类似于蛋氨酸(满足)。CySeH可能分解到H(2),因此甲基化的CH(3)医师,(CH(3))(2),和(CH (3)) (3) (+)。在这项研究中,我们估计单一口服半数致死剂量(LD(50))为67.0毫克/公斤。我们还发现,(CH (3)) (3) Se(+)很快就产生单一的SeMet口服后在小鼠肝脏。这个结果表明快速的存在α,gamma-elimination途径。我们测量了大量的alpha-ketobutyrate, NH(3),和CH(3)医师由酶α,gamma-elimination反应肝脏的SeMet periodate-oxidized腺苷(PAD)或D, L-propargylglycine (PPG)治疗老鼠为了验证的存在α,gamma-elimination酶。垫的抑制剂S-adenosylhomocysteinase (EC 3.3.1.1), SeCyH SeMet转换是必要的。分是一种有效的抑制剂的吡哆醛5 '磷酸(PLP)包含酶细菌L-methionine gamma-lyase (EC 4.4.1.11)导致了α,gamma-elimination SeMet反应和胱硫醚gamma-lyase (EC 4.4.1.1)有关转换SeMet SeCyH。当SeMet孵化与S9分数从PAD-treated小鼠肝脏,alpha-ketobutyrate的形成一样,从参与小鼠肝脏。 However, the amount of alpha-ketobutyrate formed significantly decreased in the reaction of SeMet with S9 fraction from the liver of PPG-treated mice. In an in vivo experiment using mice treated with PAD before a toxic dosage of SeMet, the amount of SeMet in the liver decreased and the amount of acid-volatile Se derived from CH(3)SeH increased gradually. This phenomenon was not observed in the PPG-pretreated group. Furthermore, the protein fraction that had the alpha,gamma-elimination enzyme activity was found in mouse liver cytosol by gel chromatographic technique. The results of this study indicated that SeMet was directly metabolized to CH(3)SeH by an alpha,gamma-elimination enzyme analogous to bacterial L-methionine gamma-lyase, in addition to the generally acceptable pathway via SeCyH.

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药物靶点

药物	目标	类	生物	药理作用	行动
磷酸吡哆醛	胱硫醚gamma-lyase	蛋白质	人类	未知的	代数余子式	细节