Abstract
C-terminal α-amidation of peptides is an important event in the course of pro-hormone and neuropeptide processing; it is a modification that contributes to the biological activity and stability of about 25 peptides in neural and endocrine systems. This laboratory has shown that bovine growth hormone (bGH) also has a catalytic function, i.e. peptidylglycine monooxygenase activity, which is the first step in the alpha-amidation of glycine-extended peptides. We report here that the peptidylglycine monooxygenase activity of monomeric bovine pituitary GH, in the presence of ascorbate, is stimulated by combination with oligomeric forms of bGH one of which is a hetero-oligomer with metallothionein. Three species of recombinant monomeric GH (bovine, human and chicken) also catalyze this monooxygenase reaction. Tetrahydrobiopterin also functions as a reductant - with a significantly greater turnover than achieved with ascorbate. These findings clarify the role of GH in peptidylglycine monooxygenation and provide an explanation for earlier observations that peptide amidation is not totally obliterated in the absence of ascorbate, in cultured pituitary cells or in vivo. The evolution of bifunctional GH is also discussed, as are some of the significances of the peptidylglycine monooxygenase activity of human GH in relation to peptides such as oxytocin, glucagon-like peptide-1 and peptide PYY.