title: Rhythmic nucleotide synthesis in the liver: temporal segregation of metabolites.
abstract: 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.
authors: Department of System Biology, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-Shimo-Adachi-cho, Kyoto 606-8501, Japan.
authors: Jean-Michel
authors: JM
authors: Fustin
authors: Masao
authors: M
authors: Doi
authors: Hiroyuki
authors: H
authors: Yamada
authors: Rie
authors: R
authors: Komatsu
authors: Shigeki
authors: S
authors: Shimba
authors: Hitoshi
authors: H
authors: Okamura
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002940:Circadian Rhythm; D008099:Liver / Q000378:metabolism*; D055442:Metabolome; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism; D008957:Models, Genetic; D009711:Nucleotides / Q000096:biosynthesis* / Q000378:metabolism; D010766:Phosphorylation; D011687:Purines / Q000096:biosynthesis / Q000378:metabolism; D011743:Pyrimidines / Q000096:biosynthesis / Q000378:metabolism; D014527:Uric Acid / Q000378:metabolism
chemical_list: D009711:Nucleotides; D011687:Purines; D011743:Pyrimidines; D014527:Uric Acid; D000255:Adenosine Triphosphate