Metabolic Dissipative Structures - Systems Biology of Metabolic and Signaling Networks - page 180

reversible interactions between multienzyme complexes and other molecular
structures. This may lead to the formation of metabolic microcompartmentation
and channeling resulting from a discrete reactive space where intermediate
metabolites can be protected from being consumed by competing reactions (Milani
et al. 2003 ). Elsewhere, we have referred as metabolic subsystems these self-
organized multienzymatic complexes, which can be associated with other
noncatalytic biomolecular structures, in which oscillations and quasi-steady-state
patterns can spontaneously emerge (De la Fuente 2010 ). Thermodynamically,
metabolic subsystems represent advantageous biochemical organizations, forming
unique, well-defined autonomous dynamic systems (De la Fuente 2010 ).
Nonlinear kinetics, catalytic irreversibility, and the coupling between nonlinear
reactions and diffusion are main source of spatiotemporal self-organization in
metabolic subsystems (Goldbeter 2007 ; Nicolis and Prigogine 1977 ). A rich variety
of dynamic patterns emerging from these metabolic subsystems can be associated
with distinct activity regimes, independent of direct genomic control (De la Fuente
et al. 2013 ).
Overall, a metabolic subsystem constitutes an elemental macromolecular
machine, a catalytic module, which provides an efficient enzymatic activity.
Associations between metabolic subsystems can form higher level complex molec-
ular organizations, as for example it occurs with intracellular energetic units
(ICEU) (Saks et al. 2006 ) and synaptosomes (Monge et al. 2008 ).
8.1.4 Dissipative Metabolic Networks
Structural observations have shown that, in cells, the overall enzymatic organiza-
tion is given by modules of multienzyme complexes arrayed as a network (Gavin
et al. 2002 ). Moreover, the cellular metabolic system behaves like a multi-
oscillatory system (Lloyd 2005 ; Lloyd and Murray 2005 , 2006 ; Murray
et al. 2007 ; Roussel and Lloyd 2007 ; Vanin and Ivanov 2008 ) comprising mito-
chondrial, nuclear, transcriptional, and metabolic dynamics (Lloyd et al. 2006 ). In
this context, redox rhythmicity has been suggested as a fundamental dynamic hub
for intracellular temporal coherence (Lloyd and Murray 2007 ).
To address the function of cellular metabolism from the point of view of self-
organization, the dissipative metabolic network (DMN) concept was proposed
(De la Fuente et al. 1999a , 2008 ). Essentially, a DMN is a set of metabolic
subsystems interconnected by substrate fluxes and three classes of regulatory
signals: activatory (positive allosteric modulation), inhibitory (negative allosteric
modulation), and all-none type, e.g., enzyme regulation by covalent modification.
In a DMN, the output activity for each metabolic subsystem can be either steady
state or predominantly oscillatory with different activity regimes.
The first model of a DMN put in evidence a singular systemic metabolic
structure, characterized by a set of different metabolic subsystems always locked
into active states (metabolic core) while the rest of the catalytic subsystems