Compartmentation metabolites

It has long been recognised that metabolites, and metabolic activities, are distributed non-uniformly within cells. Such compartmentation is undoubtedly an important aspect of metabolic regulation. The accurate quantitation of metabolite levels in various intracellular compartments represents a major stumbling block in the study of metabolic regulation. There are two aspects to the study of metabolite compartmentation by in vivo NMR. The first, and most problematic, is the assignment of resonances to specific intracellular compartments we focus on this aspect here. The second is the use of NMR spectroscopic parameters (e.g., intensity, chemical shift) to monitor conditions (e.g., pH, concentrations, fluxes) within specific compartments, using methods outlined in other sections of this chapter. 

COMPARTMENTALIZED PYRUVATE CARBOXYLASE DEPENDS ON METABOLITE CONVERSION AND TRANSPORT The second interesting feature of pyruvate carboxylase is that it is found only in the matrix of the mitochondria. By contrast, the next enzyme in the gluconeogenic pathway, PEP carboxykinase, may be localized in the cytosol or in the mitochondria or both. For example, rabbit liver PEP carboxykinase is predominantly mitochondrial, whereas the rat liver enzyme is strictly cytosolic. In human liver, PEP carboxykinase is found both in the cytosol and in the mitochondria. Pyruvate is transported into the mitochondrial matrix, where it can be converted to acetyl-CoA (for use in the TCA cycle) and then to citrate (for fatty acid synthesis see Figure 25.1). /Uternatively, it may be converted directly to 0/ A by pyruvate carboxylase and used in glu-... 

J. Guern, J. P. Renaudin, S. C. Brown, The compartmentation of secondary metabolites in plant cell cultures. Cell Culture and Somatic Cell Genetics of Plants. Vol. 4 (F, Constabel and 1. K. Vasil, eds.). Academic Press, San Diego, 1987, p. 43. A. L. Samuels, M. Fernando, and A. D. M. Glass, Immunofluorescent localization of plasma membrane H -ATPase in barley roots and effects of K nutrition. Plant Physiol. 99 1509 (1992). 

Berl, S., Nicklas, W. J. and Clarke, D. D. Compartmentation of citric acid cycle metabolism in brain labelling of glutamate, glutamine, aspartate and gaba by several radioactive tracer metabolites. J. Neurochem. 17 1009-1015, 1970. 

Wink M (1997) Compartmentation of secondary metabolites and xenobiotics in plant vacuoles. In Leigh RA, Sanders D, Callow JA (eds) The plant vacuole advances in botanical research, vol 25. Academic, London, pp 141-169... 

For biochemical reactions, the stoichiometric coefficients are usually integer and correspond to the (relative) molecularities in which the reactants enter the reaction. Note that for transport processes, and unless metabolites are measured in absolute quantities, the stoichiometric coefficient also reflect differences in compartmental volumes. 

One of several general models for metabolite compart-mentation in which a central compartment is directly linked to or feeds from (hence the name) other compartments that do not communicate with each other aside from their connection to the central pool. See Catenary Model Compartmental Analysis... 

The labeled form of a metabolite, drug, or other substance used in a kinetic analysis of tracee biosynthesis/ entry (appearance) and tracee catabolism/clearance (disappearance). See Compartmental Analysis... 

A membrane is a semipermeable barrier whose function is to compartmentalize metabolic processes, maintain pH differences on either side, control osmotic pressure and ionic gradients, provide a surface or environment for the stabilization of active biomolecules, provide tissue discrimination, and allow selective access as well as egress to specific metabolites. 

Pharmacokinetic models. An important advance in risk assessment for hazardous chemicals has been the application of pharmacokinetic models to interpret dose-response data in rodents and humans (EPA, 1996a Leung and Paustenbach, 1995 NAS/NRC, 1989 Ramsey and Andersen, 1984). Pharmacokinetic models can be divided into two categories compartmental or physiological. A compartmental model attempts to fit data on the concentration of a parent chemical or its metabolite in blood over time to a nonlinear exponential model that is a function of the administered dose of the parent. The model can be rationalized to correspond to different compartments within the body (Gibaldi and Perrier, 1982). 

Proteomic analysis thus has a strong place to provide complementary and more exacting insights into cellular-level responses and provides a means to more clearly realize the basis of molecular interactions, metabolite fluxes, and outputs. Unlike mRNA, proteins cannot be amplified, are far more chemically and structurally diverse, are often compartmentalized, and have chemical features that differentially affect extraction. Thus, comprehensive... 

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