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肿瘤细胞从5'-甲硫基腺苷合成甲硫氨酸。

Methionine synthesis from 5'-methylthioadenosine by tumour cells.

作者信息

Tisdale M J

出版信息

Biochem Pharmacol. 1983 Oct 1;32(19):2915-20. doi: 10.1016/0006-2952(83)90396-9.

DOI:10.1016/0006-2952(83)90396-9
PMID:6626263
Abstract

Incubation of cytosolic fractions of some tumour and normal cell lines with 5'-methylthioadenosine (5'-MTA) resulted in the formation of methionine. Methionine formation only occurred in those cell lines possessing 5'-MTA phosphorylase. The kinetics of product formation indicated that 5'-MTA was first rapidly converted into 5-methylthioribose-1-phosphate, followed by its slower conversion into methionine. Methionine synthesis from 5'-MTA was increased in cells previously incubated in methionine-depleted medium supplemented with 0.1 mM L-homocysteine for 24 hr. For most cell lines methionine synthesis from 5'-MTA was linear for only a short time period, and was followed by a first order decrease in the rate of methionine synthesis. Methionine synthesized from 5'-MTA was extensively incorporated into cellular macromolecules suggesting that 5'-MTA may substitute for methionine as a one-carbon source. This was confirmed by growth experiments which showed that low concentrations of 5'-MTA could partially substitute for methionine for some, but not all, cell lines. Higher concentrations of 5'-MTA were growth inhibitory. It may be possible to use 5'-MTA to selectively 'rescue' cells from methionine deprivation produced by the enzyme L-methioninase.

摘要

将某些肿瘤细胞系和正常细胞系的胞质组分与5'-甲硫腺苷(5'-MTA)一起温育会生成甲硫氨酸。甲硫氨酸的生成仅发生在那些具有5'-MTA磷酸化酶的细胞系中。产物生成的动力学表明,5'-MTA首先迅速转化为5-甲硫基核糖-1-磷酸,随后再缓慢转化为甲硫氨酸。在预先于补充有0.1 mM L-同型半胱氨酸的甲硫氨酸缺乏培养基中温育24小时的细胞中,由5'-MTA合成甲硫氨酸的量增加。对于大多数细胞系而言,由5'-MTA合成甲硫氨酸仅在短时间内呈线性,随后甲硫氨酸合成速率呈一级下降。由5'-MTA合成的甲硫氨酸被广泛掺入细胞大分子中,这表明5'-MTA可能作为一碳源替代甲硫氨酸。生长实验证实了这一点,该实验表明低浓度的5'-MTA可以部分替代甲硫氨酸用于某些(但不是所有)细胞系。较高浓度的5'-MTA具有生长抑制作用。有可能使用5'-MTA从由L-甲硫氨酸酶产生的甲硫氨酸剥夺中选择性地“挽救”细胞。

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