×

Variable elimination in post-translational modification reaction networks with mass-action kinetics. (English) Zbl 1256.92019

Summary: We define a subclass of chemical reaction networks called post-translational modification systems. Important biological examples of such systems include MAPK cascades and two-component systems which are well-studied experimentally as well as theoretically. The steady states of such a system are solutions to a system of polynomial equations. Even for small systems the task of finding the solutions is daunting. We develop a mathematical framework based on the notion of a cut (a particular subset of species in the system), which provides a linear elimination procedure to reduce the number of variables in the system to a set of core variables. The steady states are parameterized algebraically by the core variables, and graphical conditions for when steady states with positive core variables imply positivity of all variables are given. Further, minimal cuts are the connected components of the species graph and provide conservation laws. A criterion for when a (maximal) set of independent conservation laws can be derived from cuts is given.

MSC:

92C42 Systems biology, networks
92C45 Kinetics in biochemical problems (pharmacokinetics, enzyme kinetics, etc.)
05C90 Applications of graph theory
80A30 Chemical kinetics in thermodynamics and heat transfer

References:

[1] Angeli D, De Leenheer P, Sontag E (2010) Graph-theoretic characterizations of monotonicity of chemical networks in reaction coordinates. J Math Biol 61: 581–616 · Zbl 1204.92038 · doi:10.1007/s00285-009-0309-0
[2] Cooper GM, Hausman RE (2009) The cell, 5th edn. ASM Press, Washington
[3] Cornish-Bowden A (2004) Fundamentals of enzyme kinetics, 3rd edn. Portland Press, London
[4] Craciun G, Feinberg M (2005) Multiple equilibria in complex chemical reaction networks. I. The injectivity property. SIAM J Appl Math 65(5): 1526–1546 · Zbl 1094.80005 · doi:10.1137/S0036139904440278
[5] Diestel R (2005) Graph theory, graduate texts in mathematics, vol 173, 3rd edn. Springer, Berlin
[6] Feinberg M (1980) Lectures on chemical reaction networks 1. pp 1–18. http://www.che.eng.ohio-state.edu/\(\sim\)feinberg/LecturesOnReactionNetworks/
[7] Feinberg M (1987) Chemical reaction network structure and the stability of complex isothermal reactors I. The deficiency zero and deficiency one theorems. Chem Eng Sci 42(10): 2229–2268 · doi:10.1016/0009-2509(87)80099-4
[8] Feinberg M, Horn FJM (1977) Chemical mechanism structure and the coincidence of the stoichiometric and kinetic subspaces. Arch Ration Mech Anal 66(1): 83–97 · Zbl 0384.70026 · doi:10.1007/BF00250853
[9] Feliu E, Wiuf C (2011a) Enzyme sharing as a cause of multistationarity in signaling systems. J R Soc Interf doi: 10.1098/rsif.2011.0664 (epub ahead of print, Nov 2)
[10] Feliu E, Wiuf C (2011b) Variable elimination in chemical reaction networks with mass action kinetics. arXiv 1109.1505 · Zbl 1251.92050
[11] Feliu E, Knudsen M, Andersen LN, Wiuf C (2012) An algebraic approach to signaling cascades with n layers. Bull Math Biol 74(1): 45–72 · Zbl 1244.92015 · doi:10.1007/s11538-011-9658-0
[12] Gross JL, Yellen J (2006) Graph theory and its applications, 2nd edn. Discrete mathematics and its applications. Chapman and Hall/CRC, Boca Raton · Zbl 1082.05001
[13] Heinrich R, Neel BG, Rapoport TA (2002) Mathematical models of protein kinase signal transduction. Mol Cell 9: 957–970 · doi:10.1016/S1097-2765(02)00528-2
[14] Huang CY, Ferrell JE (1996) Ultrasensitivity in the mitogen-activated protein kinase cascade. Proc Natl Acad Sci USA 93: 10078–10083 · doi:10.1073/pnas.93.19.10078
[15] Kholodenko BN, Birtwistle MR (2009) Four-dimensional dynamics of MAPK information processing systems. Wiley Interdiscip Rev Syst Biol Med 1: 28–44 · doi:10.1002/wsbm.16
[16] King E, Altman C (1956) A schematic method of deriving the rate laws for enzyme-catalyzed reactions. J Phys Chem 60: 1375–1378 · doi:10.1021/j150544a010
[17] Krell T, Lacal J, Busch A, Silva-Jimenez H, Guazzaroni ME, Ramos JL (2010) Bacterial sensor kinases: diversity in the recognition of environmental signals. Annu Rev Microbiol 64: 539–559 · doi:10.1146/annurev.micro.112408.134054
[18] Markevich NI, Hoek JB, Kholodenko BN (2004) Signaling switches and bistability arising from multisite phosphorylation in protein kinase cascades. J Cell Biol 164: 353–359 · doi:10.1083/jcb.200308060
[19] Ostman A, Bohmer FD (2001) Regulation of receptor tyrosine kinase signaling by protein tyrosine phosphatases. Trends Cell Biol 11: 258–266 · doi:10.1016/S0962-8924(01)01990-0
[20] Thomson M, Gunawardena J (2009) The rational parameterization theorem for multisite post-translational modification systems. J Theor Biol 261: 626–636 · Zbl 1403.92085 · doi:10.1016/j.jtbi.2009.09.003
[21] Tutte WT (1948) The dissection of equilateral triangles into equilateral triangles. Proc Camb Philos Soc 44: 463–482 · Zbl 0030.40903 · doi:10.1017/S030500410002449X
[22] Ventura AC, Sepulchre JA, Merajver SD (2008) A hidden feedback in signaling cascades is revealed. PLoS Comput Biol 4:e1000041
This reference list is based on information provided by the publisher or from digital mathematics libraries. Its items are heuristically matched to zbMATH identifiers and may contain data conversion errors. In some cases that data have been complemented/enhanced by data from zbMATH Open. This attempts to reflect the references listed in the original paper as accurately as possible without claiming completeness or a perfect matching.