Acetylation of decarboxylated S-adenosylmethionine by mammalian cells.
Acetylation of decarboxylated S-adenosylmethionine by mammalian cells.
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DOI：
10.1021/bi00350a016
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发表时间：
1986-01
期刊：
影响因子：
2.9
通讯作者：
A. Pegg;R. Wechter;R. Clark;L. Wiest;B. Erwin
中科院分区：
文献类型：
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作者：
A. Pegg;R. Wechter;R. Clark;L. Wiest;B. Erwin
脱羧 S-腺苷甲硫氨酸被发现是作用于多胺和组蛋白的核乙酰转移酶的底物。在饱和底物浓度下，脱羧S-腺苷甲硫氨酸的乙酰化率是亚精胺的两倍以上，并且脱羧S-腺苷甲硫氨酸是大鼠肝脏核提取物组蛋白乙酰化的活性抑制剂。在暴露于鸟氨酸脱羧酶抑制剂 2-(二氟甲基)鸟氨酸的 SV-3T3 细胞中，脱羧 S-腺苷甲硫氨酸发生体内乙酰化。发现暴露于2-(二氟甲基)鸟氨酸引起的腐胺和亚精胺的下降伴随着脱羧S-腺苷甲硫氨酸和乙酰化脱羧S-腺苷甲硫氨酸的含量大幅上升。这些结果表明，脱羧S-腺苷甲硫氨酸不仅在作为多胺生物合成的氨丙基供体的众所周知的反应中被代谢，而且还通过与乙酰辅酶A反应中的乙酰化而被代谢。此外，脱羧S-腺苷甲硫氨酸对组蛋白乙酰化的抑制可能有助于鸟氨酸脱羧酶抑制剂带来的生物效应。
Decarboxylated S-adenosylmethionine was found to be a substrate for the nuclear acetyltransferases that act on polyamines and on histones. The rate of acetylation of decarboxylated S-adenosylmethionine was more than twice that of spermidine at saturating substrate concentrations, and decarboxylated S-adenosylmethionine was an active inhibitor of the acetylation of histones by nuclear extracts from rat liver. The acetylation of decarboxylated S-adenosylmethionine occurred in vivo in SV-3T3 cells exposed to the ornithine decarboxylase inhibitor 2-(difluoromethyl)ornithine. The decline in putrescine and spermidine brought about by exposure to 2-(difluoromethyl)ornithine was found to be accompanied by a large rise in the content of both decarboxylated S-adenosylmethionine and acetylated decarboxylated S-adenosylmethionine. These results indicate that decarboxylated S-adenosylmethionine is metabolized not only in the well-known reactions in which it serves as an aminopropyl donor for polyamine biosynthesis but also by acetylation in reaction with acetyl coenzyme A. Furthermore, the inhibition of histone acetylation by decarboxylated S-adenosylmethionine could contribute to the biological effects brought about by inhibitors of ornithine decarboxylase.