Metabolism metabolite concentration

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. 

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... 

In contrast, SKM does not assume knowledge of thespecific functional form of the rate equations. Rather, the system is evaluated in terms of generalized parameters, specified by the elements of the matrices A and 0X. In this sense, the matrices A and 0 x are bona fide parameters of the system The pathway is described in terms ofan average metabolite concentration S°, and a steady-state flux vector v°, together defining the metabolic state of the pathway. Additionally, we assume that the substrate only affects reaction v2, the saturation matrix is thus fully specified by a single parameter Of 6 [0,1], Note that the number of parameters is identical to the number used within the explicit equation. The structure of the parameter matrices is... 

The metabolic state of the minimal model is specified by one independent flux value v° and 3 steady-state metabolite concentrations,... 

Once the matrix of dependencies is specified, the model is evaluated at a given metabolic state, characterized by 18 metabolite concentrations and 4 independent flux values. The numerical values for concentrations and fluxes are adopted from Ref. [113], describing the pathway under conditions of light and... 

Based on a previously constructed model, two crucial questions with respect to dynamic properties were investigated [296] (i) What is the role of feedback regulation in maintaining the stability of the steady state. In particular, does the feedback regulation contribute to a stabilization of the in vivo metabolic state (ii) Is it possible to distinguish between different metabolic states That is, does knowledge of the metabolic state, characterized by the flux distribution and metabolite concentrations, indeed constrain the dynamic properties of the system ... 

A. Hoppe, S. Hoffmann, and H. G. Holzhiitter, Including metabolite concentrations into flux balance analysis Thermodynamic realizability as a constraint on flux distributions in metabolic networks. BMC Syst. Biol. 1, 23 (2007). 

The changes in metabolite concentrations in human blood, urine, or other appropriate biological media over time may be useful in estimating phenol s rate of metabolism in humans. In some instances, the quantification of metabolites may be useful in correlating the exposure doses to the human body burden. Studies that correlate phenol exposure with levels of metabolites in human biological matrices are not available for this compound, although analytical methods for the quantification of the metabolites are available. 

A computer program for calculating steady-state fluxes and metabolite concentrations of metabolic systems on the IBM-PC and compatible computers. The software provides a simple means for calculating the control structure of a pathway. 

Published human data are summarized in Table 6.3. Although the maximum concentration achieved transiently varies to some extent with PPT subclass and matrix in which it is consumed, it is unlikely that plasma metabolite concentrations will routinely exceed 10 pMin total, and 1 lM for total aglycones. The reported Tjnax values range from 1 to 2.5 h for substances absorbed in the duodenum,up to 5 to 12 h when microbial metabolism is a prerequisite.Published elimination half-lives are very variable, ranging from as low as 1 to values in excess of 20 i57,i5s,i6o values may be artifacts of... 

Hoey, L., Rowland, I.R., Lloyd, A.S., Clarke, D.B., and Wiseman, H., Influence of soya-based infant formula consumption on isoflavone and gut microflora metabolite concentrations in urine and on faecal microflora composition and metabolic activity in infants and children, Br. J. Nutr, 91, 607, 2004. 

Non-invasive P MRS has become one of the most useful tools to investigate in vivo muscle metabolism since the first muscle P MRS study reported by Hoult et al. in 1974. Many muscle P MRS studies in human or animal models have been reported and reviewed. For example, recently Kemp and his co-workers reported a quantitative review of phosphorus metabolite concentrations in human muscle. Here, we... 

During fasting, hormonal or metabolic modifications mobilise energy stored in adipose tissue as fat. Evaluation of different metabolite concentrations in blood provides insight into the different steps of fat metabolism. 

However, the embryo or fetus may have the ability to metabolize the compound itself or further metabolize metabolites. This is especially the case in humans where the fetal liver at mid-gestation has 20% to 40% of adult activity for phase 1 reactions. If the metabolites produced by the embryo or fetus are polar or large, they may become trapped inside the embryonic system as they will be unable to diffuse across the placenta into the maternal bloodstream. Similarly, if the compound or metabolites entering the embryo bind to or react with proteins or other macromolecules, this process may effectively entrap the compound inside the embryonic system. Either of these processes may cause a concentration gradient to exist across the placenta and will prolong embryonic or fetal exposure to the compound. 

Review of the use of NMR to measure metabolite concentrations during glycogen synthesis, interpreted by metabolic control analysis. 

All the techniques described in this chapter contribute to improved metabolite characterization. Notably, these techniques will enable the generation of extended time profiles for plasma radioactivity, the assessment of free metabolite concentrations following plasma dialysis, and the characterization of metabolites at very low levels of exposure, for example, following inhaled or dermal routes of administration. Furthermore, the use of high-sensitivity techniques could impact the design of radiolabel studies, for example, by enabling a lower radiolabel dose to be administered to human subjects without compromising the ability to characterize the metabolic fate of the compound of interest. 

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