导读：日本研究人员通过动物实验发现，肝脏内传递基因信息的核苷酸，按照生物钟以一定的节奏合成。研究人员希望据此开发出将癌症化疗与生物钟节奏结合的治疗方法，改善治疗效果。
核苷酸是核酸的基本组成单位，随着核酸分布于生物体内各器官、组织和细胞中，并作为核酸的组成成分参与生物的遗传、发育、生长等基本生命活动。
京都大学教授冈村均率领的研究小组在新一期美国《细胞—报告》上发表论文说，他们在动物实验中使用破坏了肝脏内生物钟的小鼠和正常小鼠，调查了核苷酸生成的酶的变化。结果发现正常小鼠白天酶的生成量是夜间的四分之一左右，其量的变化是有规律的，大致呈抛物线状，而体内生物钟被破坏的小鼠，酶量的变化则是混乱的。
酶的变化反映了核苷酸量的变化。由于癌症化疗就是通过改变核苷酸所产生酶的量来杀死癌细胞的，研究人员认为，弄清核苷酸合成的节奏，有助于在治疗癌症时选择最合适的时机进行化疗，从而改善治疗效果并降低副作用。
Rhythmic Nucleotide Synthesis in the Liver: Temporal Segregation of Metabolites
Jean-Michel Fustin, Masao Doi, Hiroyuki Yamada, Rie Komatsu, Shigeki Shimba, Hitoshi Okamura
The synthesis of nucleotides in the body is centrally controlled by the liver, via salvage or de novo synthesis. We reveal a pervasive circadian influence on hepatic nucleotide metabolism, from rhythmic gene expression of rate-limiting enzymes to oscillating nucleotide metabolome in wild-type (WT) mice. Genetic disruption of the hepatic clock leads to aberrant expression of these enzymes, together with anomalous nucleotide rhythms, such as constant low levels of ATP with an excess in uric acid, the degradation product of purines. These results clearly demonstrate that the hepatic circadian clock orchestrates nucleotide synthesis and degradation. This circadian metabolome timetable, obtained using state-of-the-art capillary electrophoresis time-of-flight mass spectrometry, will guide further investigations in nucleotide metabolism-related disorders.
文献链接：https://www.cell.com/cell-reports/abstract/S2211-1247(12)00072-1
