Analysis of progress curves for enzyme-catalysed reactions. Automatic construction of computer programs for fitting integrated rate equations.

In epithelial cells isolated from rat small intestine, we have studied the influence of vasoactive intestinal peptide (VIP), a neurotransmitter which markedly increases enterocyte cyclic AMP, and of two cyclic AMP analogues (8-bromo cyclic AMP and N6,2'-O-dibutyryl cyclic AMP) on the rate of glycolysis, fructose 2,6-bisphosphate concentration and 6-phosphofructo-2-kinase activity, as well as on the rate of 3-O-methyl-D-[14C]glucose uptake. Our results show that, without affecting the rate of 3-O-methyl-D-[14C]glucose accumulation, VIP and cyclic AMP analogues were able to inhibit glucose consumption and L-lactate formation by isolated rat enterocytes. These effects occurred parallel to a significant decrease in the cellular concentration of fructose 2,6-bisphosphate and to a partial inactivation of 6-phosphofructo-2-kinase. These findings support the hypothesis that VIP inhibits glycolysis in rat enterocytes through a cyclic AMP-dependent mechanism.