Specificity of a serum peptidase hydrolyzing thyroliberin at pyroglutamyl-histidine bone

The substrate specificity of a serum enzyme which degrades thyroliberin (less than Glu-His-Pro-NH2) into pyroglutamic acid and His-Pro-NH2 has been investigated and compared with that of the pyroglutamyl aminopeptidase from calf liver. The latter enzyme has a broad specificity, causing rapid degradation of thyroliberin, pyroglutamyl beta-naphthylamide and luliberin. In contrast, the serum enzyme causes rapid stereospecific cleavage only of the pyroglutamyl-histidine bond of thyroliberin and closely related peptides. Compounds such as less than Glu-Ala, less than Glu-His and pyroglutamyl beta-naphthylamide, which are known substrates of the pyroglutamyl aminopeptidases (such as the liver enzyme), are not substrates of the serum enzyme, and inhibit it only poorly. Pyroglutamyl-containing peptides such as luliberin and neurotensin and thyroliberin analogues such as LLD-thyroliberin, less than Glu-His-Pro-NHCH3, less than Glu-His-Pro-Gly-NH2 and less than Glu-Phe-Pro-NH2 inhibit effectively the degradation of thyroliberin by the serum enzyme, but are not hydrolyzed by this enzyme. The high specificity of the serum enzyme implies a physiological function.