蛋氨酸/ S -腺苷甲硫氨酸循环活性由核激素受体感知和调节。
methionine/S-adenosylmethionine cycle activity is sensed and adjusted by a nuclear hormone receptor.
机构信息
Program in Systems Biology and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, United States.
Department of Biochemistry and Molecular Biophysics, Columbia University, New York, United States.
出版信息
Elife. 2020 Oct 5;9:e60259. doi: 10.7554/eLife.60259.
Vitamin B12 is an essential micronutrient that functions in two metabolic pathways: the canonical propionate breakdown pathway and the methionine/S-adenosylmethionine (Met/SAM) cycle. In low vitamin B12, or genetic perturbation of the canonical propionate breakdown pathway results in propionate accumulation and the transcriptional activation of a propionate shunt pathway. This propionate-dependent mechanism requires and is referred to as 'B12-mechanism-I'. Here, we report that vitamin B12 represses the expression of Met/SAM cycle genes by a propionate-independent mechanism we refer to as 'B12-mechanism-II'. This mechanism is activated by perturbations in the Met/SAM cycle, genetically or due to low dietary vitamin B12. B12-mechanism-II requires to activate Met/SAM cycle gene expression, the vitamin B12 transporter, , and adjust influx and efflux of the cycle by activating and repressing , respectively. Taken together, Met/SAM cycle activity is sensed and transcriptionally adjusted to be in a tight metabolic regime.
维生素 B12 是一种必需的微量营养素，它在两条代谢途径中发挥作用：经典的丙酸分解途径和蛋氨酸/ S-腺苷甲硫氨酸（Met/SAM）循环。在维生素 B12 水平低或经典丙酸分解途径的遗传干扰下，会导致丙酸积累，并激活丙酸分流途径的转录。这种依赖于丙酸的机制需要，并被称为“B12 机制-I”。在这里，我们报告维生素 B12 通过一种我们称为“B12 机制-II”的与丙酸无关的机制来抑制 Met/SAM 循环基因的表达。这种机制是由 Met/SAM 循环的干扰激活的，无论是遗传上还是由于饮食中维生素 B12 水平低。B12 机制-II 需要 来激活 Met/SAM 循环基因的表达，维生素 B12 转运蛋白 ，并通过激活 和抑制 ，分别调整循环的流入和流出，从而调整 Met/SAM 循环基因的表达。总之，Met/SAM 循环的活性被感知，并进行转录调整以维持严格的代谢状态。
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