The role of cyclic GMP in the regulation of cyclic AMP hydrolysis

Abstract

A rat-heart cyclic nucleotide phosphodiesterase has been chromatographically separated from related enzymes and its kinetic properties have been studied. The enzyme can hydrolyze both cyclic AMP and cyclic GMP and has about the same maximum velocity and apparent KM (greater than 10-5 M) for the two nucleotides. Kinetic plots indicate positive cooperative behavior for both substrates. Cyclic GMP at low concentrations is a potent activator of cyclic AMP hydrolysis and this activation, as well as the cooperativity, can be abolished by treatment with solvents or sulfydryl reagents under conditions which do not destroy the catalytic function. A kinetic model for this enzyme is porposed and the physiologic role is discussed.