by Khlebodarova T.M. | Akberdin I.R. | Kozlov K.N. | Kazantsev F.V. | Fadeev S.I. | Likhoshvai V.A. |
Institute Cytology and Genetics SB RAS | Department of Systems Biology, Institute of Cytology and
Genetics SB RAS, Novosibirsk, Russia; Department of Natural Sciences, Novosibirsk State University,
Novosibirsk, Russia; Department of Computational Biology, Sirius University of Science and Technology,
Sochi, Russia; Biosoft.RU LTD, Novosibirsk, Russia. | 6Higher School for Applied Mathematics and
Computational Physics, PhysMech, Peter the Great St. Petersburg Polytechnic University, St. Petersburg,
Russia | Department of Systems Biology, Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia;
Department of Natural Sciences, Novosibirsk State University, Novosibirsk, Russia | Institute of
Mathematics SB RAS, Novosibirsk, Russia; Deceased | Department of Systems Biology, Institute of
Cytology and Genetics SB RAS, Novosibirsk, Russia; Deceased
Background: Previous studies aimed to investigate the metabolism of endogenous
nucleoside triphosphates in synchronous E. coli cell cultures demonstrated an existence of
the self-oscillatory mode of the functioning of pyrimidines and purines biosynthesis. Authors
of these studies associated the dynamic behavior with cell division. The metabolic system
theoretically has an internal oscillatory potential due to feedback mechanisms orchestrating
its dynamics. The question of whether the nucleotide biosynthesis system has its own
oscillatory circuit is still open.
Results: To solve this issue, an integral mathematical model of pyrimidine biosynthesis was
developed, which explores all experimentally verified negative feedbacks in the regulation
of enzymatic reactions, data on detection under in vitro conditions. An analysis of the
dynamic modes of the model functioning showed the possibility of implementing both
stationary and oscillating modes of functioning in the pyrimidine biosynthesis system for
certain sets of kinetic parameters that fit within the physiological boundaries of the
metabolic system under study. It was shown that the occurrence of an oscillating nature of
the synthesis of metabolites depended on the ratio of two parameters: the Hill coefficient,
which is the nonlinearity of the influence of UMP on the activity of carbamoylphosphate
synthetase, and the parameter r, which characterizes the contribution of the noncompetitive
mechanism of UTP inhibition to the regulation of the enzymatic reaction of UMP
phosphorylation.
Conclusions: It was suggested that the system of pyrimidines biosynthesis in E. coli has its
own oscillatory mode the potential of that substantially depends on the mechanisms of UMP
kinase’s activity.