REDUCED AVAILABILITY OF ENDOGENOUSLY SYNTHESIZED METHIONINE FOR S-ADENOSYLMETHIONINE FORMATION IN METHIONINE-DEPENDENT CANCER-CELLS
REDUCED AVAILABILITY OF ENDOGENOUSLY SYNTHESIZED METHIONINE FOR S-ADENOSYLMETHIONINE FORMATION IN METHIONINE-DEPENDENT CANCER-CELLS
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DOI：
10.1073/pnas.79.14.4248
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发表时间：
1982-01-01
期刊：
影响因子：
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通讯作者：
HOFFMAN, RM
中科院分区：
文献类型：
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作者：
COALSON, DW;MECHAM, JO;HOFFMAN, RM
甲硫氨酸（Met）依赖性，即当Met被其直接前体同型半胱氨酸（Met-Hcy+培养基）取代时，培养细胞无法生长，是致癌转化表型的常见组成部分。正常细胞在这种培养基中生长。已经有报道称，Met依赖性细胞中Met生物合成的速率正常或更高，并且假设Met依赖性细胞缺乏利用内源性合成的Met，而不是外源性供应的Met。为了回答在Met依赖性[人癌]细胞中什么生化反应需要预先形成的Met这一关键问题，用无Met的[35 S]Hcy或[35 S]Met标记细胞，并测定Met、S-腺苷甲硫氨酸（Met）和S-腺苷高半胱氨酸（Hcy）的水平。实验证明，Met依赖性细胞内源性合成正常量的Met，并且缺乏利用该Met进行Met合成。外源性提供的Met通常用于Met的生物合成。在Met-Hcy+培养基中生长的Met依赖性细胞中，α-Met与α-Hcy的比率较低，但在Met+Hcy-培养基中正常。低的Met/Hcy比值可能限制了Met依赖性细胞在Met-Hcy+培养基中的生长。
Methionine (Met) dependence, the inability of cultured cells to grow when Met is replaced by its immediate precursor homocysteine (Met-Hcy+ medium), is a frequent component of the oncogenically transformed phenotype. Normal cells, on the other hand, grow in this medium. There have been reports of normal or higher rates of Met biosynthesis in Met-dependent cells and a postulation that Met-dependent cells are deficient in utilization of endogenously synthesized Met as opposed to exogenously supplied Met. To answer the critical question of what biochemical reactions require preformed Met in Met-dependent [human cancer] cells, cells were labeled with Met-free [35S]Hcy or [35S]Met and determined the levels of Met, S-adenosylmethionine (AdoMet) and S-adenosylhomocysteine (AdoHcy). Experiments demonstrate that Met-dependent cells synthesize a normal amount of Met endogenously and are deficient in utilizing this Met for AdoMet synthesis. Exogenously supplied Met is utilized normally for AdoMet biosynthesis. The ratio of AdoMet to AdoHcy is low in Met-dependent cells growing in Met-Hcy+ medium but is normal in Met+Hcy- medium. The low AdoMet/AdoHcy ratio probably limits growth of Met-dependent cells in Met-Hcy+ medium.