REGULATION OF GLYCOLYSIS VIA REVERSIBLE ENZYME BINDING TO THE MEMBRANE-PROTEIN, BAND-3

Most metabolic pathways are regulated by feedback inhibition/activatio n or by covalent modification of a regulatory enzyme. In erythrocytes, however, we demonstrate that glycolysis can be modulated over 30-fold by controlling the availability of glycolytic enzyme binding sites at the extreme N terminus of the anion transporter, band 3. Direct obstr uction of these inhibitory sites by anti-peptide Fab's against residue s 1-15 of band 3 promotes an approximately 3-fold increase in the rate of lactate production. In contrast, enrichment of the erythrocyte cyt oplasm with the band 3 peptide against which the above antibodies were raised results in a more than 10-fold decrease in the rate of lactate accumulation. Control peptides and their derived antipeptide antibodi es corresponding to other sequences of band 3 or glycophorin were foun d to have no effect on lactate production. Analysis of changes in glyc olytic intermediates during Fab treatments suggests that hexokinase ma y be one enzyme that is modulated by association with band 3. We concl ude that the extreme N terminus of band 3 can bind and inhibit glycoly tic enzymes in vivo and that it probably participates in control of re d cell glycolysis.