Proenkephalin (PENK), formerly known as proenkephalin A (since proenkephalin B was renamed prodynorphin), is an endogenous opioid polypeptide hormone which, via proteolyic cleavage, produces the enkephalin peptides [Met]enkephalin, and to a lesser extent, [Leu]enkephalin.[5] 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.[5] 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,[6] amidorphin,[7] BAM-18,[8] BAM-20P,[9] BAM-22P,[9] peptide B,[10] peptide E,[11] and peptide F.[12]
Proenkephalin is produced by the medium spiny neurons of the striatum which undergo neurodegeneration in early stages of Huntington's disease (HD). PENK[13] and related peptides[14][15] measured in cerebrospinal fluid are proposed as potential biomarkers of disease progression in HD.