Specificity of a Serum Peptidase Hydrolyzing Thyroliberin at the Pyroglutamyl‐Histidine Bond

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Abstract
The substrate specificity of a serum enzyme which degrades thyroliberin (< 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 β‐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 < Glu‐Ala, < Glu‐His and pyroglutamyl β‐naphthylamide, which are known substrates of the pyroglutamyl atninopeptidases (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, < Glu‐His‐Pro‐NHCH3, < Glu‐His‐Pro‐Gly‐NH2 and < 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.