Opioids pp 529-545 | Cite as

Opioid Peptide Processing Enzymes

  • L. D. Fricker
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 104 / 1)


The biosynthesis of the opioid peptides is generally similar to the biosynthesis of many other peptide hormones and neurotransmitters. The bioactive peptides are initially produced as larger precursors which require posttranslational processing by several enzymes (Table 1). A necessary step for the production of most bioactive peptides is the limited proteolytic cleavage of the precursor by one or more endopeptidases which selectively cleave the precursor at specific sites, usually pairs of basic amino acids. In some cases, these cleavage sites are single basic amino acids. Following the endopeptidase action, a carboxypeptidase is required to remove the cleavage site residues from the C-terminus of the peptides. In addition to these proteolytic steps, some opioid peptides undergo other posttranslational modifications including sulfation, phosphorylation, glycosylation, N-terminal acetylation, and C-terminal amidation. Some of these modifications appear to be required for biological activity and/or stability of the peptide. All of these posttranslational modifications are performed inside the cell, prior to secretion. Once the peptides are secreted, they are exposed to extracellular enzymes. Some of the extracellular enzymes inactivate the opioid peptides, while other enzymes cleave the peptides into smaller fragments which retain opioid activity. In many cases, the differential processing, both intracellular and extracellular, leads to peptides with distinct biological activities. Thus, the enzymes that process opioid peptides play a key role in the generation of specific messengers.


Secretory Granule Basic Amino Acid Opioid Peptide Basic Residue Bioactive Peptide 
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© Springer-Verlag Berlin Heidelberg 1993

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  • L. D. Fricker

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