Proenkephalin


Proenkephalin, formerly known as proenkephalin A, is an endogenous opioid polypeptide hormone which, via proteolyic cleavage, produces the enkephalin peptides met-enkephalin, and to a lesser extent, leu-enkephalin. Upon cleavage, each proenkephalin peptide results in the generation of four copies of Met-enkephalin, two extended copies of met-enkephalin, and one copy of leu-enkephalin. Contrarily, Leu-enkephalin is predominantly synthesized from prodynorphin, which produces three copies of it per cleavage, and no copies of Met-enkephalin. Other endogenous opioid peptides produced by proenkephalin include adrenorphin, amidorphin, BAM-18, BAM-20P, BAM-22P, peptide B, peptide E, and peptide F.
The following table lists the peptides that are derived from cleavage of the proenkephalin protein.
PeptideAlternative NamesAmino acid positions
Met-enkephalinOpioid growth factor 107–111
PENKNeuropeptide E; ENK-20114–133
Leu-enkephalin—150–154
Met-enkephalin-Arg-PheMERF; Neuropeptide AF186–191
Met-enkephalin-Arg-Gly-LeuMERGL; Neuropeptide AM218–223
PENKNeuropeptide F237–258

Clinical significance

Proenkephalin is produced by the medium spiny neurons of the striatum which undergo neurodegeneration in early stages of Huntington's disease. PENK and related peptides measured in cerebrospinal fluid are proposed as potential biomarkers of disease progression in HD. Furthermore, PENK has been found associated with acute kidney injury and glomerular filtration rate in steady-state and critically ill patients.