Heterogeneity of kinetic parameters of enzymes in situ in rat liver lobules.

In the present review, metabolic compartmentation in liver lobules is discussed as being dynamic and more complex than thus far assumed on the basis of numbers of mRNA or protein molecules or the capacity (zero-order activity) of enzymes. Isoenzyme distribution patterns and local kinetic parameters of enzymes may vary over the different zones of liver lobules. As a consequence, metabolic fluxes in vivo at physiological substrate concentrations may be completely different from those that are assumed on the basis of the number of molecules or the capacity of enzymes present in zones of liver lobules. For a more correct estimation of the levels of metabolic processes in the different compartments of liver tissue, local kinetic parameters and substrate concentrations have to be determined to calculate local metabolic fluxes. Direct measurements of metabolic fluxes in vivo with the use of noninvasive techniques is a promising alternative and the techniques will become increasingly important in future metabolic research.