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Proenkephalin

Protein-coding gene in the species Homo sapiens

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. 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.

Peptide	Alternative Names	Amino acid positions
Met-enkephalin	Opioid growth factor (OGF)	107–111
PENK(114–133)	Neuropeptide E; ENK-20	114–133
Leu-enkephalin	—	150–154
Met-enkephalin-Arg-Phe	MERF; Neuropeptide AF	186–191
Met-enkephalin-Arg-Gly-Leu	MERGL; Neuropeptide AM	218–223
PENK(237–258)	Neuropeptide F	237–258

Clinical significance

Proenkephalin is produced by the medium spiny neurons of the striatum which undergo neurodegeneration in early stages of Huntington's disease (HD). 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.

References

Donald W. Pfaff. (2002). "Hormones, brain, and behavior". Elsevier.
(1983). "Novel C-terminally amidated opioid peptide in human phaeochromocytoma tumour". Nature.
(1985). "Isolation and structure of a novel C-terminally amidated opioid peptide, amidorphin, from bovine adrenal medulla". Nature.
(June 1987). "Pharmacological properties of a proenkephalin A-derived opioid peptide: BAM 18". European Journal of Pharmacology.
(December 1980). "A new family of endogenous "big" Met-enkephalins from bovine adrenal medulla: purification and structure of docosa- (BAM-22P) and eicosapeptide (BAM-20P) with very potent opiate activity". Biochemical and Biophysical Research Communications.
(1984). "Purification and sequence of a non-opioid peptide derived from ovine proenkephalin: implications for possible species specific processing". Peptides.
(December 1987). "Peptide E and its products, BAM 18 and Leu-enkephalin, in bovine adrenal medulla and cultured chromaffin cells: release in response to stimulation". Journal of Neurochemistry.
(October 1980). "Structure of two adrenal polypeptides containing multiple enkephalin sequences". Archives of Biochemistry and Biophysics.
(April 2001). "Involvement of pro-enkephalin-derived peptides in immunity". Developmental and Comparative Immunology.
(February 2021). "Proenkephalin Decreases in Cerebrospinal Fluid with Symptom Progression of Huntington's Disease". Movement Disorders.
(February 1989). "Decrease in a proenkephalin peptide in cerebrospinal fluid in Huntington's disease and progressive supranuclear palsy". Brain Research.
(September 2022). "Cerebrospinal fluid levels of proenkephalin and prodynorphin are differentially altered in Huntington's and Parkinson's disease". Journal of Neurology.
(December 2023). "Proenkephalin as a biomarker correlates with acute kidney injury: a systematic review with meta-analysis and trial sequential analysis". Critical Care.
(November 2023). "Assessing GFR With Proenkephalin". Kidney International Reports.
(September 2020). "Proenkephalin Compared to Conventional Methods to Assess Kidney Function in Critically Ill Sepsis Patients". Shock.

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opioids neuropeptides precursor-proteins

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