Metabolite concentrations

Because substrate cycles such as this appear to operate with no net benefit to the cell, they were once regarded as metabolic quirks and were referred to as futile cycles. More recently, substrate cycles have been recognized as important devices for controlling metabolite concentrations. 

Measurements of metabolite concentrations in muscle fibers before and after fatiguing stimulation have shown that ATP decreases from 6 to 4.6 mM and PCr decreases from 35 to 2.4 mM with a calculated increase in Pj from 3 to 38 mM (Dawson et al., 1978 Nassar-Gentina et al., 1978). The free ADP concentration was calculated to increase from 30 to 200 pM. At the same time pH decreased from 7.0 to 6.5 (Dawson et al., 1978 Juel, 1988 Westerblad and Lannergren, 1988). The effect of these metabolic changes has been studied in skinned muscle fibers, i.e., fibers in which the cell membrane has been removed. The skinning of the fibers... 

Here the effects of any one fractionating step can be expressed in a change in isotopic composition in a wider range of body tissue components, including the product as well as the precursor of a (reversible) reaction. The details depend on the explicit model, for example how rates depend on metabolite concentrations. Therefore, where a metabolic pathway is, or becomes, reversible, the effect on isofractionation on measured body components can be more widespread. 

An update of a previous study (Axelson et al. 1978), Axelson (1986) evaluated an expanded cohort of 1,424 men (levels of trichloroethylene exposure inferred from measured urinary metabolite concentrations) and found a significant increase in incidences of bladder cancer and lymphomas, and a lower than expected incidence of total cancer mortality. A further update of this work (Axelson et al. 1994) expanded the cohort to include 249 women, tracking cancer morbidity over 30 years, and found no correlation between exposure concentration or exposure time and cancer incidence at any site. The highest standardized incidence ratio noted in this study was 1.56 (95% Cl of 0.51-3.64) for 5 cases of non-Hodgkin s lymphoma observed in men. Although four of these cases occurred in persons exposed for at least 2 years, and 3 cases had a latency of 10 years or more, urinary levels of TCA showed that 4 of the 5 cases were exposed to the lowest levels of trichloroethylene (urinary levels of TCA 0-49 mg/L). The study authors mentioned that a urinary TCA level below 50 mg/L corresponds to a trichloroethylene exposure concentration of about 20 ppm. The study authors concluded that "this study provides no evidence that trichloroethylene is a human carcinogen, i.e., when the exposure is as low as for this study population."... 

Schroeder, W. and Bohm, H., Once more secondary metabolite concentrations in whole plants and in cell cultures derived therefrom, J. Plant Physiol, 145,126,1995. Yang, R.Y.K. et al., Plant-cell bioreactors with simultaneous electropermeabilization and electrophoresis, J. BiotechnoL, 100, 13, 2003. 

The total radioactivity in serum (PCP and metabolites) increased significantly after Fab administration (figure 4). This increase was mostly due to the dramatic increase in unchanged PCP concentration and not due to an increase in metabolite concentration. 

Brand Name) Active Metabolites Concentration (hour) Range (hour) Dosage Range (mg/day) Equivalent (mg)... 

The design of a study by Davies et al. (1982) for mixers and applicators was similar to that of Nigg and Stamper (1983). "Between-days" variances of exposure were not given. Mean urinary metabolite concentrations were used to show reduction of internal exposure by protective clothing. The design of the study by van Rooij et al. (1993) was similar to our study (i.e., "within-worker" comparisons of internal exposure). Because no potential dermal exposure was assessed in this study, "within-worker" variances of potential exposure are not known. 

In a study of workers exposed to -hexane (Mutti et al. 1984), the post-exposure alveolar excretion of -hexane was about 10% of the total uptake, and was in 2 phases a fast phase with a half-life of 11 minutes and a slow phase with a half-life of 99 minutes. Urinary metabolite concentrations were lowest at the beginning of the shift, highest at the end of the shift, and still elevated the next morning. Half-life for urinary excretion of total -hexane metabolites (2,5-dimethylfuran, 2-hexanol,... 

Studies that address the site of production, the transport, and the deposition of secondary metabolites provide another level of resolution that needs to be considered when evaluating the function of secondary metabolites and their patterns of distribution. Unlike approaches that quantify an alga s total metabolite concentration, studies that localize metabolites contained within algal tissues provide evidence of more subtle changes in metabolite distribution in response to stimuli and may clarify metabolite function. 

Vascular plants are known to induce a variety of phenotypic changes in response to damage, including changes in secondary metabolite concentrations. Induced plant responses may lead to increased resistance toward future herbivory if changes have... 

An interesting vertical profile of the metabolite concentrations was observed the compounds showed a tendency to accumulate at the two-phase boundaries of air-freshwater and freshwater-saline water (the halocline). Thus, concentration maxima were observed at depths of 0 and 2 m (see Fig. 6.4.1) [6]. The observed distribution may result from either the physicochemical properties of these compounds (surface activity and hydrophobicity), or their formation at the interface due to increased biological activity. For the parent surfactants a similar but less pronounced vertical distribution pattern was observed (with maxima at 0 and 2 m of 17 and 9 xg L 1, respectively) [5],... 

Of nine estuaries investigated in England by Blackburn et al., only the sediments from the highly industrialised Tees estuary contained detectable concentrations of NP and A9PEOi+2 [12]. In this estuary, also the highest APEO metabolite concentrations in water were found. GC-MS analysis showed maximum sediment concentrations of 1.7 pgg-1 NP and 3.6 pg g-1 A9PEOi+2. 

Equation (5) describes the variation of a metabolite concentration over time as proportional to the rates in which a metabolite is synthesized minus the rates at which it is consumed. A stationary and time-invariant state of metabolite concentrations S° (steady state) is characterized by the steady-state condition... 

The values for metabolite concentrations are needed at different occasions for modeling metabolism (i) as an additional data source to validate kinetic models that are constructed in a bottom-up approach, (ii) as starting point for steady-state search algorithms, (iii) as additional experimental data for... 

Stoichiometric analysis goes beyond topological arguments and takes the specific physicochemical properties of metabolic networks into account. As noted above, based on the analysis of the nullspace of complex reaction networks, stoichiometric analysis has a long history in the chemical and biochemical sciences [59 62]. At the core of all stoichiometric approaches is the assumption of a stationary and time-invariant state of the metabolite concentrations S°. As already specified in Eq. (6), the steady-state condition... 

Huege et al. [271] cultivated Arabidopsis plants in 13C02 atmosphere, transferred the plants to normal atmosphere, and monitored the dilution of isotopes in several metabolite pools. Through evaluation of the mass isotopomer distribution, metabolite partitioning processes could be monitored. However, due to the lack of absolute metabolite concentrations, no absolute fluxes could be calculated. Nevertheless, building upon this method, suitable approaches for flux analysis in autotrophic tissue might be derived in the future. 

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