Transport metabolons with carbonic anhydrases

THE CONCEPT OF THE TRANSPORT METABOLON A metabolon has been defined as a “temporary, structural-functional, supramolecular complex of sequential metabolic enzymes and cellular structural elements, in which metabolites are passed from one active site to another without complete equilibration with the bulk cellular fluids” (Srere, 1985, 1987). This substrate channeling should decrease transit time of intermediates, prevent loss of intermediates by diffusion, protect labile intermediates from solvent, and prevent entrance of intermediates into competing metabolic pathways (Miles et al., 1999). Such metabolons have been found in many metabolic pathways like glycolysis and tricarboxylic acid cycle, as well as in the biosynthesis of DNA, RNA, and proteins (Srere, 1987). Some of the major acid/base-coupled membrane transporters, such as the Cl−/HCO3 exchanger AE1 (anion exchanger 1; Band3), the Na+/H+ exchanger NHE1, the Na+/HCO3 cotransporter NBCe1, and various monocarboxylate transporters (MCTs) have been demonstrated to physically and/or functionally interact with isoforms of carbonic anhydrase (CA) to form a “transport metabolon.” This functional interaction includes an increase in transport activity, and therefore may enhance both the rate and the capacity of ion/metabolite transport in tissues where these membrane transporters and enzymes are co-localized.