Ability of cofactors to support peptide amidation is cell-type specific.

The ability of various cofactors to substitute for ascorbate in the biosynthesis of alpha-aidated peptides from pro-ACTH/endorphin (PAE) was compared in corticotrope tumor cells (AtT-20) and in primary anterior and intermediate pituitary cultures. In all three systems, ascorbate was the most potent cofactor tested. In AtT-20 cells, dopamine, norepinephrine, epinephrine, dehydroascorbate and dihydro- and tetrahydrobiopterin supported significant alpha-amidation of joining peptide [PAE(77-94)NH2]. In contrast, amidation of joining peptide by primary corticotropes was stimulated only slightly by catecholamines and not by tetrahydrobiopterin. Neither catecholamines nor tetrahydrobiopterin stimulated peptide amidation by melanotropes. The ability of cofactors to support the synthesis of alpha-amidated peptides is cell-type specific.