Zusammenfassung
The history of the development of the ideas and research of organized
metabolic systems during last three decades is shortly reviewed.
The cell cytoplasm is crowded with solutes, soluble macromolecules
such as enzymes, nucleic acids, structural proteins and membranes.
The high protein density within the large compartments of the cells
predominantly determines the major characteristics of cellular environment
such as viscosity, diffusion and inhomogeneity. The fact that the
solvent viscosity of cytoplasm is not substantially different from
the water is explained by intracellular structural heterogeneity:
the intrinsic macromolecular density is relatively low within the
interstitial voids in the cell because many soluble enzymes are apparently
integral parts of the insoluble cytomatrix and are not distributed
homogeneously. The molecular crowding and sieving restrict the mobility
of very large solutes, binding severely restrict the mobility of
smaller solutes. One of consequence of molecular crowding and hindered
diffusion is the need to compartmentalize metabolic pathway to overcome
diffusive barriers. Although the movement of small molecules is slowed
down in the cytoplasm, the metabolism can successfully proceed and
even be facilitated by metabolite channeling which directly transfers
the intermediate from one enzyme to an adjacent enzyme without the
need of free aqueous-phase diffusion. The enhanced probability for
intermediates to be transferred from one active site to the other
by sequential enzymes requires stable or transient interactions of
the relevant enzymes, which associate physically in non-dissociable,
static multienzyme complexes--metabolones, particles containing enzymes
of a part or whole metabolic systems. Therefore, within the living
cell the metabolism depends on the structural organization of enzymes
forming microcompartments. Since cells contain many compartments
and microenvironments, the measurement of the concentration of metabolites
in whole cells or tissues gives an average cellular concentration
and not that which is actually sensed by the active site of a specific
enzyme. Thus, the microcompartmentation could provide a mechanism
which can control metabolic pathways. Independently and in parallel
to the developments described above, the ideas of compartmentation
came into existence from the necessity to explain important physiological
phenomena, in particular in heart research and in cardiac electrophysiology.
These phenomena demonstrated the physiological importance of the
biophysical and biochemical mechanisms described in this review.
Nutzer