ABSTRACT
Opioid peptides and other neuropeptides are initially produced as larger precursors that undergo post-translational modifications and proteolytic cleavages to produce bioactive peptides. The various post-translational processing steps occur in specific parts of the cell as the peptide is transported from the site of translation (the endoplasmic reticulum) through the Golgi apparatus and regulated secretory pathway, and finally secreted into the extracellular environment. A large number of enzymes are involved in the post-translational processing of peptides (Table 5.1). Thefirstevent is the removal of the 'signal peptide', the targeting signal for transport into the endoplasmic reticulum (ER). This processing step occurs in the ER while the protein is being translated. Proteins with N-linked carbohydrates are glycosylated in the ER while those proteins with O-linked carbohydrates are glycosylated in the Golgi apparatus. Further processing of the carbohydrate side chains occurs in the Golgi, along with phosphorylation and/or sulfation. Proteolytic processing of the peptide precursor begins in the latter part of the Golgi, named the 'trans Golgi networks' (TGN). Further proteolytic processing occurs as the precursors are packaged into secretory vesicles of the regulated pathway. After proteolytic processing, some peptides are further modified or, the N-and/or C-termini by acetylation and amidation, respectively. These modifications occur inside the vesicles, prior to secretion. After the peptides are secreted, additional proteolytic processing enzymes cleave the peptide. In many cases, the extracellular processing does not destroy the bioactivity of the peptide, but alters the receptor affinity and/or specificity.
