title: Generic temperature compensation of biological clocks by autonomous regulation of catalyst concentration.
abstract: Circadian clocks--ubiquitous in life forms ranging from bacteria to multicellular organisms--often exhibit intrinsic temperature compensation; the period of circadian oscillators is maintained constant over a range of physiological temperatures, despite the expected Arrhenius form for the reaction coefficient. Observations have shown that the amplitude of the oscillation depends on the temperature but the period does not; this suggests that although not every reaction step is temperature independent, the total system comprising several reactions still exhibits compensation. Here we present a general mechanism for such temperature compensation. Consider a system with multiple activation energy barriers for reactions, with a common enzyme shared across several reaction steps. The steps with the highest activation energy rate-limit the cycle when the temperature is not high. If the total abundance of the enzyme is limited, the amount of free enzyme available to catalyze a specific reaction decreases as more substrates bind to the common enzyme. We show that this change in free enzyme abundance compensates for the Arrhenius-type temperature dependence of the reaction coefficient. Taking the example of circadian clocks with cyanobacterial proteins KaiABC, consisting of several phosphorylation sites, we show that this temperature compensation mechanism is indeed valid. Specifically, if the activation energy for phosphorylation is larger than that for dephosphorylation, competition for KaiA shared among the phosphorylation reactions leads to temperature compensation. Moreover, taking a simpler model, we demonstrate the generality of the proposed compensation mechanism, suggesting relevance not only to circadian clocks but to other (bio)chemical oscillators as well.
authors.affiliation: Department of Basic Science, Graduate School of Arts and Sciences, University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo, 153-8902, Japan.
authors.forename: Tetsuhiro S
authors.initials: TS
authors.lastname: Hatakeyama
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Kaneko
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology; D001426:Bacterial Proteins / Q000502:physiology*; D055162:Biocatalysis; D001683:Biological Clocks / Q000502:physiology*; D001833:Body Temperature Regulation / Q000502:physiology*; D056925:Circadian Rhythm Signaling Peptides and Proteins / Q000502:physiology*; D000458:Cyanobacteria / Q000502:physiology*; D004734:Energy Metabolism / Q000502:physiology; D004798:Enzymes / Q000378:metabolism; D008954:Models, Biological; D010766:Phosphorylation / Q000502:physiology; D013696:Temperature
chemical_list: D001426:Bacterial Proteins; D056925:Circadian Rhythm Signaling Peptides and Proteins; D004798:Enzymes; C114269:KaiA protein, cyanobacteria; C114270:KaiB protein, cyanobacteria; C114271:KaiC protein, cyanobacteria