Metabolites production rate

The foremost requirement is the accurate determination of an observable bioreaction network structure that describes indene oxidation in Rhodococcus. Based on product accumulation profiles and induction studies, indene bioconversion networks have been proposed for several isolates [8]. To validate further these networks for our strains and employ them for flux analysis we developed an experimental system that can maintain cells at steady state while allowing accurate metabolite measurements for flux determination. The system comprised a chemostat with a regular feed of hquid medium and separate supply of the indene precursor through a gas phase hne. Indene uptake and metabolite production rates were easily measured in this system, leading to the calculation of the unknown bioconversion fluxes. Additional measurements for system closure and further validation were obtained by using radiolabeled tracers and measuring the products of their oxidation in Rhodococcus cultures [9,10]. 

The increase with temperature of substrate uptake, yeast growth and flocculation, and metabolite production rate is simply described by Arrhenius type of relationships. 

The 2006 draft FDA guidance for drug interactions suggests that in vitro studies should be conducted to identify drug metabolizing enzymes if the metabolic pathway contributes more than 25% of a drug s clearance based on human in vivo data. Whenever possible, these in vitro experiments should be conducted with drug concentrations deemed appropriate by kinetic experiments. Enzyme identification experiments should be conducted under initial rate conditions, where the linearity of metabolite production rate is assumed... 

In order to develop a rational approach to improving rates of metabolite production, it is necessary to consider the fate of the nutrients that are required for its synthesis. However, overcoming the major flux control points within a metabolic pathway may not lead to metabolite overproduction if the energetic consequences of the alteration are unfavourable to the organism. 

It is obvious that rapid metabolite production requires high fluxes of carbon through the metabolic systems responsible for its synthesis. The rate of metabolite production, for a wide range of micro-organisms, has been shown to increase with decrease in... 

In dass 1 (ATP requiring), the rate of metabolite production is limited by the micro-organisms capacity to dissipate energy. 

In dass 2 (ATP generating), the rate of metabolite production, and oxidation state, are inversely related to the growth effidency. 

In dass 3, the rate of metabolite production from a single substrate may be limited by the rate of ATP turnover. Provision of ready made precursors can increase both the metabolite yield (final concentration) and rate of production by decreasing the requirement for ATP turnover during biosynthesis. 

The effect of a particular cultivation environment on a system can be evaluated in terms of biomass (fresh/dry weight, cell number), secondary metabolite production [51,75,89,102,103,106,107] or substrate consumption (e.g. carbon source [57] or oxygen [53,108]). Using the Evan s Blue method to identify non-viable cells. Ho et al. [108] used viable cell density measurements to determine variations in specific growth rate attributable to hydrodynamic stress. 

GULF TOADFISH, Opsanus tau Isolated hepatocytes acclimatized to 18 or 28°C, then exposed to BaP at 18, 23, or 28°C for about 2 h Isolated gill cells acclimatized to either 18 or 28°C for 3 weeks and exposed for 8 h to 1-100 mg BaP/L at incubation temperatures of 18, 23, and 28°C Dose-dependent increase in metabolite production. 23 Rapid metabolism of BaP independent of temperature Accumulation followed a dose-concentration gradient 24 uptake rate was higher for cells acclimatized to 18°C than those acclimatized to 28°C at all incubation temperatures. When cells were exposed to BaP at the respective acclimatization temperatures, uptake rates were similar... 

Prostacyclin, a potent inhibitor of platelet aggregation, is derived from metabo-lisation of arachidonic acid by endothelial cells, and shear stress increases its production rate [12]. It is postulated that this effect is due to perturbations of the permeability of the plasma membrane changing the cytosolic Ca + content and leading to an increase in phospholipase C activity (through the by-passing of the receptor requirement), which contributes to a higher production of arachidonic metabolites. 

There is also strong evidence indicating that there is an inverse relationship between growth rate and secondary metabolite production (Lindsey and Yeoman, 1983). When growth is intense, the primary processes of the cell are cell division and production of cell mass. In the stationary phase, when growth is minimal, conditions favor the production and accumulation of secondary metabolites. 

Metabolite Production. Strain variations to hexobarbital are often dependant on its degradation rate. For example, male mice of the AL/N strain are long sleepers, and this trait is correlated with slow inactivation of the drug. The reverse is true in CFW/N mice, which have short sleeping time due to rapid hexobarbital oxidation. This close relationship is further evidenced by the fact that the level of brain hexobarbital at awakening is essentially the same in all stains. Similar strain differences have been reported for zoxazolamine paralysis in mice. 

Plants are known as a potential source of a large number of important biochemical constituents (1-3). In recent years, transformed hairy roots have been studied as a potential large-scale source for production of plant-derived useful compounds such as pharmaceuticals. They have several advantages compared to plant cell suspension culture, such as high growth rate, high and stable secondary metabolite productivity, autotrophy of... 

The identification of phenomena that explain the behavior of a studied system depends on the analysis of their kinetic data. Normally, this kinetic analysis is performed using characteristic variables calculated from the experimental data. The specific rates and the yield coefficients are the common values used in this task. When cell concentration data are available, cell growth and death rates, as well as cell viability, are the best kinetic variables to characterize the population physiological state. In the absence of this information - as can occur, for example, with immobilized cells - the treatment must be based on substrate consumption or on metabolites production (Miller and Reddy, 1998). 

---