  Fission yeast G2/M transition is regulated by a biochemical reaction networks
which contains four components: Cdc13, Cdc2, Wee1, and Cdc25. This circuit is
characterized by the ultrasensitive responses of Wee1 or Cdc25 to Cdc13/Cdc2
activity, and the bistability of Cdc2 activation. Previous work has shown that
this bistability is governed by phosphorylation energy. In this article, we
developed the kinetic model of this circuit and conducted further thermodynamic
analysis on the role of phosphorylation energy (&[Delta]G). We showed that
level &[Delta]G shapes the response curves of Wee1 or Cdc25 to Cdc2 and governs
the intrinsic noise level of Cdc2 activity. More importantly, the mutually
antagonistic chemical fluxes around the PdP cycles in G2/M circuit were shown
to act as a stabilizer of Cdc2 activity against &[Delta]G fluctuations. These
results suggests the fundamental role of free energy and chemical fluxes on the
sensitivity, bistability and robustness of G2/M transition.
