山梨医科学雑誌　第22巻3号　039-057(2007)

＜Review＞
Energy-Metabolism Oscillation in the Living Organisms
with Circadian Rhythms

Kunio TSURUGI

Abstract: It has been generally accepted that the circadian rhythms are genetically controlled by circadian clocks consisting of a transcriptional/post-translational feedback-loop of circadian proteins. In contrast, yeast, which lacks circadian rhythms and clock protein homologues, shows an ultradian rhythm of energy-metabolism oscillation (EMO) with a periodic change of the predominantly anabolic and catabolic phases. EMO is comprised of a feedback loop of oxido-reductive reactions mediated by metabolites like NADH, ATP, and acetyl-CoA which periodically fluctuate in their intracellular levels in concert with the metabolic change; yeast synthesizes storage carbohydrates like glycogen and trehalose in the anabolic phase under reductive conditions and degrades them through cAMP production in the catabolic phase under predominantly oxidative conditions. So, to explore the possibility that EMO underlies the circadian rhythms, I reviewed findings in biochemical and behavioralstudies of circadian rhythms of mamma s and cyanobacteria. Many lines of evidence show that daily changes in the daily oscillation of energy metabolism between the anabolic and catabolic states are operated in both species in coupling with the metabolism of glycogen mainly through the cAMPtransduction pathway. Further, in mammals, the master pacemakers in the brain are engaged in the metabolic coordination among various peripheral tissues through hormonal and neural signal-transduction pathways which are in turn regulated by signals produced in the peripheral tissues like glucose, insulin, and catabolic hormones. Further, it seems likely that the circadian clock oscillates with a circadian periodicity by itself sensing the redox state of the cell and entrains the metabolic oscillator gives a time signal to a network of gene expression. Finally, I propose that all living organisms are autopoietic dissipative structures, that is, self-productive structures driven by the sustained oscillator EMO dissipating energy.

Key words: energy-metabolism oscillation, circadian rhythm, circadian clock, dissipative structure,
autopoiesis



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