Enzyme-to-enzyme channelling in the early steps of glycolysis in rat pancreatic islets

The metabolism of D-glucose displays anomeric specificity in rat pancreatic islets. The aim of the present report is to investigate whether such a situation implies enzyme-to-enzyme tunnelling of metabolites in the early steps of glycolysis. For such a purpose, the modelling of alpha- and beta-D-glucose catabolism, itself based on available information concerning both the utilisation of these two anomers and the intrinsic properties of phosphoglucoisomerase, was first examined. According to a theoretical model with enzyme-to-enzyme channelling, the generation of (HOH)-H-3 from D-[2-H-3]glucose should be higher in islets exposed to beta-D-glucose rather than alpha-D-glucose, whilst the opposite situation should prevail in the case of D-[5-H-3]glucose conversion to (HOH)-H-3. Experimental data collected in rat islets incubated for 60 min at 4 degreesC in the presence of either alpha- or beta-D-glucose mixed with tracer amounts of either alpha- or beta-D-[2-H-3]glucose and alpha- or beta-D-[5-H-3]glucose indicate that the beta/alpha ratio for D-[2-H-3]glucose conversion to (HOH)-H-3 is indeed higher than the beta/alpha ratio for D-[5-H-3]glucose conversion to (HOH)-H-3. These findings are consistent with the postulated enzyme-to-enzyme tunnelling of glycolytic intermediates between hexokinase isoenzyme(s), phosphoglucoisomerase and, possibly, phosphofructokinase. (C) 2004 Elsevier Ltd. All rights reserved.