title: Attractor metabolic networks.
abstract: BACKGROUND
  The experimental observations and numerical studies with dissipative metabolic networks have shown that cellular enzymatic activity self-organizes spontaneously leading to the emergence of a Systemic Metabolic Structure in the cell, characterized by a set of different enzymatic reactions always locked into active states (metabolic core) while the rest of the catalytic processes are only intermittently active. This global metabolic structure was verified for Escherichia coli, Helicobacter pylori and Saccharomyces cerevisiae, and it seems to be a common key feature to all cellular organisms. In concordance with these observations, the cell can be considered a complex metabolic network which mainly integrates a large ensemble of self-organized multienzymatic complexes interconnected by substrate fluxes and regulatory signals, where multiple autonomous oscillatory and quasi-stationary catalytic patterns simultaneously emerge. The network adjusts the internal metabolic activities to the external change by means of flux plasticity and structural plasticity.
  
  
  RESULTS
  In order to research the systemic mechanisms involved in the regulation of the cellular enzymatic activity we have studied different catalytic activities of a dissipative metabolic network under different external stimuli. The emergent biochemical data have been analysed using statistical mechanic tools, studying some macroscopic properties such as the global information and the energy of the system. We have also obtained an equivalent Hopfield network using a Boltzmann machine. Our main result shows that the dissipative metabolic network can behave as an attractor metabolic network.
  
  
  CONCLUSIONS
  We have found that the systemic enzymatic activities are governed by attractors with capacity to store functional metabolic patterns which can be correctly recovered from specific input stimuli. The network attractors regulate the catalytic patterns, modify the efficiency in the connection between the multienzymatic complexes, and stably retain these modifications. Here for the first time, we have introduced the general concept of attractor metabolic network, in which this dynamic behavior is observed.
authors.affiliation: Quantitative Biomedicine Unit, BioCruces Health Research Institute, Barakaldo, Basque Country, Spain. mtpmadei@ehu.es
authors.forename: Ildefonso M
authors.initials: IM
authors.lastname: De la Fuente
authors.forename: Jesus M
authors.initials: JM
authors.lastname: Cortes
authors.forename: David A
authors.initials: DA
authors.lastname: Pelta
authors.forename: Juan
authors.initials: J
authors.lastname: Veguillas
mesh_terms: D004926:Escherichia coli / Q000378:metabolism*; D016480:Helicobacter pylori / Q000378:metabolism*; D055442:Metabolome / Q000502:physiology*; D008954:Models, Biological
references.citation: Acta Biotheor. 1998 Mar;46(1):37-51
references.pmid: 9558751
references.citation: PLoS One. 2011;6(11):e27224
references.pmid: 22125607
references.citation: Physiol Meas. 2002 Feb;23(1):R1-38
references.pmid: 11876246
references.citation: Proc Biol Sci. 2004 Nov 7;271(1554):2305-10
references.pmid: 15539357
references.citation: PLoS One. 2009 Oct 19;4(10):e7510
references.pmid: 19888419
references.citation: Nucleic Acids Res. 2010 Jan;38(Database issue):D750-3
references.pmid: 19854939
references.citation: Biosystems. 2007 Feb;87(2-3):215-23
references.pmid: 17188804
references.citation: Science. 2010 Jan 22;327(5964):419-20
references.pmid: 20093462
references.citation: Science. 2010 Jan 22;327(5964):439-42
references.pmid: 20093467
references.citation: Nature. 2004 Feb 26;427(6977):839-43
references.pmid: 14985762
references.citation: Bull Math Biol. 1999 May;61(3):573-95
references.pmid: 17883232
references.citation: Biophys Chem. 2001 Aug 30;92(1-2):17-34
references.pmid: 11527576
references.citation: Int J Mol Sci. 2010 Sep 27;11(9):3540-99
references.pmid: 20957111
references.citation: Nat Cell Biol. 2007 Feb;9(2):130-2
references.pmid: 17268474
references.citation: Exp Cell Res. 1986 Feb;162(2):486-94
references.pmid: 3943553
references.citation: PLoS One. 2010 Mar 02;5(3):e9484
references.pmid: 20209156
references.citation: Hippocampus. 2003;13(4):494-524
references.pmid: 12836918
references.citation: Biophys J. 1997 Feb;72(2 Pt 1):866-75
references.pmid: 9017212
references.citation: Biophys Chem. 2004 Jan 1;107(1):1-5
references.pmid: 14871595
references.citation: Biophys Chem. 2007 Jul;128(2-3):253-60
references.pmid: 17513034
references.citation: Biol Cybern. 2009 Jan;100(1):11-9
references.pmid: 19002710
references.citation: Science. 2001 Sep 14;293(5537):2040-4
references.pmid: 11557880
references.citation: Nat Rev Microbiol. 2008 Sep;6(9):681-91
references.pmid: 18679172
references.citation: Nature. 2010 Oct 21;467(7318):929-34
references.pmid: 20962839
references.citation: Science. 2005 May 6;308(5723):873-6
references.pmid: 15879220
references.citation: Proc Biol Sci. 2011 Feb 22;278(1705):539-45
references.pmid: 20826487
references.citation: Nature. 2006 Mar 30;440(7084):667-70
references.pmid: 16572170
references.citation: Proc Natl Acad Sci U S A. 2010 Mar 9;107(10):4607-11
references.pmid: 20142479
references.citation: Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7328-32
references.pmid: 1831270
references.citation: Nat Struct Mol Biol. 2008 Sep;15(9):939-47
references.pmid: 19172747
references.citation: Proc Natl Acad Sci U S A. 2002 Feb 19;99 Suppl 1:2466-72
references.pmid: 11875196
references.citation: Proteomics. 2008 Feb;8(3):425-34
references.pmid: 18175372
references.citation: PLoS One. 2008 May 07;3(5):e2093
references.pmid: 18461173
references.citation: Hippocampus. 2010 Feb;20(2):235-51
references.pmid: 19405130
references.citation: Appl Microbiol Biotechnol. 2006 May;70(5):517-25
references.pmid: 16525780
references.citation: Res Microbiol. 2001 Nov;152(9):767-70
references.pmid: 11763236
references.citation: Nature. 2002 Jan 10;415(6868):141-7
references.pmid: 11805826
references.citation: Phys Rev E Stat Nonlin Soft Matter Phys. 2009 May;79(5 Pt 1):051915
references.pmid: 19518488
references.citation: J Biol Chem. 2005 Mar 25;280(12):11224-32
references.pmid: 15657047
references.citation: Phys Rev E Stat Nonlin Soft Matter Phys. 2009 Aug;80(2 Pt 1):021926
references.pmid: 19792170
references.citation: Biophys J. 1972 Oct;12(10):1302-15
references.pmid: 4263005
references.citation: Proc Natl Acad Sci U S A. 1982 Apr;79(8):2554-8
references.pmid: 6953413
references.citation: J Biol Phys. 2006 Oct;32(3-4):245-71
references.pmid: 19669466
references.citation: Nature. 2004 Oct 21;431(7011):915-6
references.pmid: 15496902
references.citation: Nature. 1969 Jun 7;222(5197):960-2
references.pmid: 5789326
references.citation: Biosystems. 1999 May;50(2):83-97
references.pmid: 10367973
references.citation: Nature. 2000 Oct 5;407(6804):651-4
references.pmid: 11034217
references.citation: Phys Rev Lett. 2008 Jan 11;100(1):018101
references.pmid: 18232821
references.citation: Biosystems. 1996;39(2):87-92
references.pmid: 8866045
references.citation: Biophys Chem. 2001 Aug 30;92(1-2):47-52
references.pmid: 11527578
references.citation: Nature. 2000 Sep 28;407(6803):470
references.pmid: 11028990
references.citation: PLoS One. 2008;3(11):e3624
references.pmid: 18982073
references.citation: Soft Matter. 2007 Dec 11;4(1):57-67
references.pmid: 32907084
references.citation: J Photochem Photobiol B. 1996 Aug;35(1-2):105-13
references.pmid: 8823940
references.citation: PLoS One. 2008 Aug 29;3(8):e3100
references.pmid: 18769681
references.citation: J Exp Biol. 2007 May;210(Pt 9):1548-58
references.pmid: 17449819
references.citation: Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):5039-44
references.pmid: 9560224
references.citation: Biophys Chem. 1996 Nov 29;62(1-3):15-24
references.pmid: 8962468
references.citation: J Biol Chem. 2002 Jul 5;277(27):24155-61
references.pmid: 11973328
references.citation: Biosystems. 1995;35(1):1-13
references.pmid: 7772719
references.citation: Nat Neurosci. 2009 Feb;12(2):190-9
references.pmid: 19169252
references.citation: Biochim Biophys Acta. 2008 Sep;1778(9):1698-713
references.pmid: 17904518
references.citation: J Neurophysiol. 2003 Feb;89(2):833-40
references.pmid: 12574461
references.citation: Neural Comput. 2010 Feb;22(2):448-66
references.pmid: 19842985
references.citation: Ann Biomed Eng. 2006 Feb;34(2):295-9
references.pmid: 16450194
references.citation: J Math Biol. 1977 Oct 20;4(4):303-21
references.pmid: 925522
references.citation: Science. 2000 Aug 11;289(5481):878-9
references.pmid: 10960319
references.citation: J Biol Phys. 2004 Mar;30(1):33-81
references.pmid: 23345861
references.citation: Biophys J. 1996 Nov;71(5):2375-9
references.pmid: 8913578
references.citation: PLoS One. 2012;7(2):e30162
references.pmid: 22393350
references.citation: PLoS Comput Biol. 2005 Dec;1(7):e68
references.pmid: 16362071
references.citation: Biophys J. 2006 May 15;90(10):L70-2
references.pmid: 16565066
references.citation: Proc Natl Acad Sci U S A. 2010 Mar 23;107(12):5267-8
references.pmid: 20332217