Metabolic Dissipative Structures - Systems Biology of Metabolic and Signaling Networks - page 177

prior diffusion into the bulk medium. Metabolic channeling decreases the transit
time of reaction substrates, thus increasing the speed and efficiency of catalysis by
preventing delays due to diffusion of reaction intermediates and their eventual loss
(Clegg and Jackson 1990; Jovanovi ´ et al. 2007 ; Jorgensen et al. 2005 ; Negrutskii
and Deutscher 1991 ; Ov ´ di and Srere 2000 ). Substrate channeling may also occur
within channels or on the electrostatic surface of enzymes belonging to complexes
(Milani et al. 2003 ; Ishikawa et al. 2004 ).
Additionally, reversible interactions between multienzyme complexes and struc-
tural proteins or membranes occur frequently in eukaryotic cells leading to the
emergence of metabolic microcompartments (Lunn 2007 ; Monge et al. 2008 , 2009 ;
Saks et al. 2007 , 2009 . Ov´di and Saks 2004 ). Microcompartments also happen in
prokaryotes, but in this case they consist of protein “shells” composed of thousands
of protein subunits, some of them being enzymes that belong to specific metabolic
pathways (Fan et al. 2010 ; Yeates et al. 2007 ). The dynamics of molecular pro-
cesses that intervene in microcompartmentation and its maintenance remain

unclear.
Multienzyme complexes, substrate channeling, and their integration into func-
tional microcompartments seem to be a central feature of the spatiotemporal
organization of cellular metabolism. This modular organization appears to be
crucial for the regulation and efficiency of enzymatic processes and thus funda-
mental for understanding the molecular architecture of life.

8.1.2 Temporal Self-Organization of Multienzymatic
Processes

Self-organization at the enzymatic level underlies the emergence of functional
structures in the temporal organization of catalytic process. Besides forming com-
plex catalytic associations, enzymes can exhibit molecular rhythms constituting a
key self-organizational trait which allow functional coordination across multiple
enzymatic complexes (De la Fuente et al. 2011 ). Cellular processes involving
biosynthesis, turnover of molecular components, migration, and division require
temporal organization across many simultaneous timescales (Chandrashekaran
2005 ; Lloyd and Murray 2005 , 2006 , 2007 ). The functional coordination implied
by metabolic rhythms involves spatial and temporal aspects of localization and
dynamics of enzymatic complexes (Hildebrandt 1982 ; Yates 1993 ; Aon and
Cortassa 1997 ; Aon et al. 2000 ), including their synchronization (Wolf et al. 2000 ).
Dynamically, cells may exhibit quasi-stationary and oscillatory states. Quasi-
stationarity arises from a slow drifting of metabolites' concentration over time. In
cells, the proportion between oscillatory and quasi-stationary states is unknown, but
existing evidence suggests that quasi-steady states are less frequent than oscillatory
ones (Lloyd and Murray 2005 ).