TY - JOUR
T1 - Opioid peptide biosynthesis
T2 - Enzymatic selectivity and regulation mechanisms
AU - Costa, E.
AU - Mocchetti, I.
AU - Supattapone, S.
AU - Snyder, S. H.
PY - 1987
Y1 - 1987
N2 - 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 carboxypeptidase B-like enzyme then removes the remaining basic amino acid. It has been unclear whether any endopeptidases with trysinlike activity are selective for one or another basic amino acid. Recently a soluble enodpeptidase 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.
AB - 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 carboxypeptidase B-like enzyme then removes the remaining basic amino acid. It has been unclear whether any endopeptidases with trysinlike activity are selective for one or another basic amino acid. Recently a soluble enodpeptidase 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.
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U2 - 10.1096/fasebj.1.1.3111927
DO - 10.1096/fasebj.1.1.3111927
M3 - Review article
C2 - 3111927
AN - SCOPUS:0023575988
SN - 0892-6638
VL - 1
SP - 16
EP - 21
JO - FASEB Journal
JF - FASEB Journal
IS - 1
ER -