Rowe W B, Meister A
Proc Natl Acad Sci U S A. 1970 Jun;66(2):500-6. doi: 10.1073/pnas.66.2.500.
The convulsant agent methionine sulfoximine inhibits brain glutamine synthetase irreversibly and the inhibitor becomes bound to the active site of the enzyme as methionine sulfoximine phosphate. Only one of the four isomers of methionine sulfoximine, L-methionine-S-sulfoximine, inhibits glutamine synthetase. In the present work, D-methionine-SR-sulfoximine, and highly purified preparations of L-methionine-S-sulfoximine and L-methionine-R-sulfoximine were tested in mice for convulsant activity; only L-methionine-S-sulfoximine produced convulsions. The finding that only one of the four optical isomers of methionine sulfoximine induces convulsions, and that only this same isomer inhibits glutamine synthetase, lends support to the conclusion that these two effects of methionine sulfoximine are closely connected.
惊厥剂蛋氨酸亚砜亚胺不可逆地抑制脑谷氨酰胺合成酶,且该抑制剂以蛋氨酸亚砜亚胺磷酸盐的形式结合到酶的活性位点上。蛋氨酸亚砜亚胺的四种异构体中只有一种,即L-蛋氨酸-S-亚砜亚胺,能抑制谷氨酰胺合成酶。在本研究中,对D-蛋氨酸-SR-亚砜亚胺以及高度纯化的L-蛋氨酸-S-亚砜亚胺和L-蛋氨酸-R-亚砜亚胺制剂在小鼠身上进行了惊厥活性测试;只有L-蛋氨酸-S-亚砜亚胺引发了惊厥。蛋氨酸亚砜亚胺的四种旋光异构体中只有一种能诱发惊厥,且只有这同一种异构体能抑制谷氨酰胺合成酶,这一发现支持了蛋氨酸亚砜亚胺的这两种作用紧密相关的结论。