Adrenocorticotropin by Mono- and Dipeptidyl Serine Carboxypeptidase Activities in Bovine Pituitary Secretory Vesicles

ACTH is a 39-amino acid peptide synthesized in the pituitary as part of the precursor molecule, POMC. Analysis of bovine anterior pituitary homogenates and secretory vesicles revealed that in addition to ACTH-(l-39), ACTH-(1-37) and ACTH-(1-38) were also present in the lobe, indicating that carboxyl-terminal processing of ACTH-(I39) occurred in viva. Mono- and dipeptidyl carboxypeptidase activities that cleaved ACTH-(l-39) were detected in bovine intermediate and anterior pituitary secretory vesicle membranes and characterized. The dipeptidyl carboxypeptidase activity liberated ACTH-(l-37) and the dipeptide, Glu-Phe, and the monocarboxypeptidase activity generated, to a smaller extent, ACTH-(l-38) and phenylalanine from ACTH-(l39). Kinetic studies indicated that the formation of ACTH-(l-37) occurred within minutes, whereas the formation of ACTH-(I-38) occurred within hours. Both enzymatic activities had a pH optimum of 5.5 and a K, of 14-18