Nonenzymatic formation of guanosine 3':5'-monophosphate from guanosine triphosphate.

We observed the nonenzymatic formation of guanosine 3’:5’-monophosphate (cyclic GMP) from GTP. The reaction was dependent upon heat and was accelerated by divalent cations and creatine phosphate. The formation of cyclic GMP was greater with increased incubation time, temperature, GTP concentration, and pH. All of the divalent cations tested (Mg2+, Mnz+, Ca2+, Ba2+, and Znzf) increased cyclic GMP formation. The stimulatory effect of all of the cations tested, except Zn2+, was increased with creatine phosphate. Cyclic GMP formed was determined with two different assay methods and characterized with cyclic nucleotide phosphodiesterase treatment and two different chromatographic systems. It is concluded from our studies that significant amounts of cyclic GMP can be formed nonenzymatically from GTP when guanylate cyclase reaction mixtures are heated at a pH near neutrality.