Opioid peptide biosynthesis: enzymatic selectivity and regulatory mechanisms.
Certain general principles determine the biosynthesis of most biologically active peptides, including the opioid peptides, from large protein precursors. In almost all instances, the active peptide is embedded in the precursor flanked on both sides by pairs of basic amino acids. The first step in processing involves a trypsinlike enzyme, cleaving to the carboxyl terminus of basic amino acids, and leaving the active peptide with a basic amino acid on the carboxyl terminus. A carboxy-peptidase peptidase B-like enzyme then removes the remaining basic amino acid. It has been unclear whether any endopeptidases with trypsinlike activity are selective for one or another basic amino acid. Recently a soluble endopeptidase has been identified that can cleave to both the carboxyl and amino termini of basic amino acids. Enkephalin convertase (carboxypeptidase E, H) (EC 3.4.17.10) has considerable selectivity, and appears to be physiologically associated with the biosynthesis of enkephalin as well as a limited number of other neuropeptides. The turnover of opioid peptides and other neuropeptides is most effectively ascertained by measuring levels of mRNA either biochemically or by in situ hybridization. Striking dynamic alterations include a pronounced increase in levels of proenkephalin mRNA in the corpus striatum after blockade of dopamine receptors, but changes in opioid peptide mRNA after opiate addiction are less clear.
D000818:Animals; D001921:Brain / Q000378:metabolism; D043423:Carboxypeptidase H; D002268:Carboxypeptidases / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism*; D004723:Endorphins / Q000096:biosynthesis* / Q000235:genetics; D004745:Enkephalins / Q000378:metabolism; D009021:Morphine Dependence / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D011954:Receptors, Dopamine / Q000187:drug effects
D004723:Endorphins; D004745:Enkephalins; D009479:Neuropeptides; D011954:Receptors, Dopamine; D002268:Carboxypeptidases; D010450:Endopeptidases; D043423:Carboxypeptidase H