Article

Regulating the cellular economy of supply and demand

Department of Biochemistry, University of Stellenbosch, Private Bag X1, Matieland 7602, South Africa.
FEBS Letters (Impact Factor: 3.34). 07/2000; 476(1-2):47-51. DOI: 10.1016/S0014-5793(00)01668-9
Source: PubMed

ABSTRACT Cellular metabolism is a molecular economy that is functionally organised into supply and demand blocks linked by metabolic products and cofactor cycles. Supply-demand analysis allows the behaviour, control and regulation of metabolism as a whole to be understood quantitatively in terms of the elasticities of supply and demand, which are experimentally measurable properties of the individual blocks. The kinetic and thermodynamic aspects of regulation are clearly distinguished. One important result is the demonstration that when flux is controlled by one block, the other block determines to which degree the concentration of the linking metabolite is homeostatically maintained.

Download full-text

Full-text

Available from: Jan-Hendrik Servaas Hofmeyr, Sep 30, 2014
0 Followers
 · 
98 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Metabolic systems are governed by a compromise between metabolic benefit and enzyme cost. This hypothesis and its consequences can be studied by kinetic models in which enzyme profiles are chosen by optimality principles. In enzyme-optimal states, active enzymes must provide benefits: a higher enzyme level must provide a metabolic benefit to justify the additional enzyme cost. This entails general relations between metabolic fluxes, reaction elasticities, and enzyme costs, the laws of metabolic economics. The laws can be formulated using economic potentials and loads, state variables that quantify how metabolites, reactions, and enzymes affect the metabolic performance in a steady state. Economic balance equations link them to fluxes, reaction elasticities, and enzyme levels locally in the network. Economically feasible fluxes must be free of futile cycles and must lead from lower to higher economic potentials, just like thermodynamics makes them lead from higher to lower chemical potentials. Metabolic economics provides algebraic conditions for economical fluxes, which are independent of the underlying kinetic models. It justifies and extends the principle of minimal fluxes and shows how to construct kinetic models in enzyme-optimal states, where all enzymes have a positive influence on the metabolic performance.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Natural genetic diversity provides a powerful resource to investigate how networks respond to multiple simultaneous changes. In this work, we profile maximum catalytic activities of 37 enzymes from central metabolism and generate a matrix to investigate species-wide connectivity between metabolites, enzymes, and biomass. Most enzyme activities change in a highly coordinated manner, especially those in the Calvin-Benson cycle. Metabolites show coordinated changes in defined sectors of metabolism. Little connectivity was observed between maximum enzyme activities and metabolites, even after applying multivariate analysis methods. Measurements of posttranscriptional regulation will be required to relate these two functional levels. Individual enzyme activities correlate only weakly with biomass. However, when they are used to estimate protein abundances, and the latter are summed and expressed as a fraction of total protein, a significant positive correlation to biomass is observed. The correlation is additive to that obtained between starch and biomass. Thus, biomass is predicted by two independent integrative metabolic biomarkers: preferential investment in photosynthetic machinery and optimization of carbon use.
    The Plant Cell 08/2010; 22(8):2872-93. DOI:10.1105/tpc.110.076653 · 9.58 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In aerobic process oxygen must be continuously supplied in order to achieve acceptable productivities, Since the role of oxygen in microorganism growth and its metabolism is of vital importance, both the oxygen consumption by the cell and the oxygen transfer rate (OTR) into the system have to be understood.The main function of a properly designed bioreactor is to provide a controlled environment and a concentration of nutrients (dissolved oxygen, mainly) sufficient to achieve optimal growth and/or optimal product formation in a particular bioprocess. Dissolved oxygen in the broths is the result of a balance of its consumption rate in the cells, and the rate of oxygen transfer from the gas to the liquid phase. Monitoring dissolved oxygen in the broth is mandatory because often oxygen becomes the factor governing the metabolic pathways in microbial cells.In this work the oxygen uptake rate (OUR) in different fermentation broths is examined. Experimental techniques have been compiled from the literature and their applicability to microbial processes reviewed. The reciprocal influence of OUR and OTR is presented and an analysis of rate-limiting variables is carried out.Mathematical models are a fundamental tool in bioprocess design, optimisation, scale-up, operation and control at large-scale fermentation. Kinetic models describing aerobic bioprocesses have to include an oxygen balance taking into account OTR and OUR. Many different specific rate expressions for cell growth, substrate consumption, product formation and oxygen uptake have been developed and incorporated in the models, and simulations of different bioprocess have been carried out. Some of them are presented here.
    Biochemical Engineering Journal 05/2010; 49(3-49):289-307. DOI:10.1016/j.bej.2010.01.011 · 2.37 Impact Factor