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Cell Rep. 2012 Apr 19;1(4):341-9. doi: 10.1016/j.celrep.2012.03.001. Epub 2012 Apr 20.

Rhythmic nucleotide synthesis in the liver: temporal segregation of metabolites.

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Department of System Biology, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-Shimo-Adachi-cho, Kyoto 606-8501, Japan.


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.

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