Proenkephalin Explained

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.[1] 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,[2] amidorphin,[3] BAM-18,[4] BAM-20P,[5] BAM-22P, peptide B,[6] peptide E,[7] and peptide F.[8]

Clinical signficance

Proenkephalin is produced by the medium spiny neurons of the striatum which undergo neurodegeneration in early stages of Huntington's disease (HD). PENK[9] and related peptides[10] [11] measured in cerebrospinal fluid are proposed as potential biomarkers of disease progression in HD. Furthermore, PENK has been found associated with acute kidney injury[12] and glomerular filtration rate in steady-state and critically ill patients.[13] [14]

See also

Notes and References

  1. Book: Donald W. Pfaff . Hormones, brain, and behavior . 25 November 2011 . 2002 . Elsevier . 978-0-12-532109-9 . 173.
  2. Matsuo H, Miyata A, Mizuno K . Novel C-terminally amidated opioid peptide in human phaeochromocytoma tumour . Nature . 305 . 5936 . 721–723 . 1983 . 6633641 . 10.1038/305721a0 . 4320171 . 1983Natur.305..721M .
  3. Seizinger BR, Liebisch DC, Gramsch C, Herz A, Weber E, Evans CJ, Esch FS, Böhlen P . Isolation and structure of a novel C-terminally amidated opioid peptide, amidorphin, from bovine adrenal medulla . Nature . 313 . 5997 . 57–59 . 1985 . 3965972 . 10.1038/313057a0 . 4363051 . 1985Natur.313...57S .
  4. Hurlbut DE, Evans CJ, Barchas JD, Leslie FM . Pharmacological properties of a proenkephalin A-derived opioid peptide: BAM 18 . European Journal of Pharmacology . 138 . 3 . 359–366 . June 1987 . 3040439 . 10.1016/0014-2999(87)90474-2 .
  5. Mizuno K, Minamino N, Kangawa K, Matsuo H . 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 . 97 . 4 . 1283–1290 . December 1980 . 7213356 . 10.1016/S0006-291X(80)80005-2 .
  6. Micanovic R, Kruggel W, Ray P, Lewis RV . Purification and sequence of a non-opioid peptide derived from ovine proenkephalin: implications for possible species specific processing . Peptides . 5 . 5 . 853–856 . 1984 . 6504720 . 10.1016/0196-9781(84)90105-0 . 3869685 .
  7. Boarder MR, Evans C, Adams M, Erdelyi E, Barchas JD . 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 . 49 . 6 . 1824–1832 . December 1987 . 3681299 . 10.1111/j.1471-4159.1987.tb02443.x . 19919675 .
  8. Jones BN, Stern AS, Lewis RV, Kimura S, Stein S, Udenfriend S, Shively JE . Structure of two adrenal polypeptides containing multiple enkephalin sequences . Archives of Biochemistry and Biophysics . 204 . 1 . 392–395 . October 1980 . 7425644 . 10.1016/0003-9861(80)90048-X .
  9. Niemela V, Landtblom AM, Nyholm D, Kneider M, Constantinescu R, Paucar M, Svenningsson P, Abujrais S, Burman J, Shevchenko G, Bergquist J, Sundblom J . Proenkephalin Decreases in Cerebrospinal Fluid with Symptom Progression of Huntington's Disease . Movement Disorders . 36 . 2 . 481–491 . February 2021 . 33247616 . 7984171 . 10.1002/mds.28391 .
  10. Iadarola MJ, Mouradian MM . Decrease in a proenkephalin peptide in cerebrospinal fluid in Huntington's disease and progressive supranuclear palsy . Brain Research . 479 . 2 . 397–401 . February 1989 . 2522341 . 10.1016/0006-8993(89)91648-X . 11033749 .
  11. Barschke P, Abu-Rumeileh S, Al Shweiki MH, Barba L, Paolini Paoletti F, Oeckl P, Steinacker P, Halbgebauer S, Gaetani L, Lewerenz J, Ludolph AC, Landwehrmeyer GB, Parnetti L, Otto M . Cerebrospinal fluid levels of proenkephalin and prodynorphin are differentially altered in Huntington's and Parkinson's disease . Journal of Neurology . 269 . 9 . 5136–5143 . September 2022 . 35737109 . 9363351 . 10.1007/s00415-022-11187-8 . 249930318 .
  12. Lin LC, Chuan MH, Liu JH, Liao HW, Ng LL, Magnusson M, Jujic A, Pan HC, Wu VC, Forni LG . Proenkephalin as a biomarker correlates with acute kidney injury: a systematic review with meta-analysis and trial sequential analysis . Critical Care . 27 . 1 . 481 . December 2023 . 38057904 . 10702091 . 10.1186/s13054-023-04747-5 . free .
  13. Beunders R, Donato LJ, van Groenendael R, Arlt B, Carvalho-Wodarz C, Schulte J, Coolen AC, Lieske JC, Meeusen JW, Jaffe AS, Pickkers P . Assessing GFR With Proenkephalin . Kidney International Reports . 8 . 11 . 2345–2355 . November 2023 . 38025210 . 10658254 . 10.1016/j.ekir.2023.08.006 .
  14. Beunders R, van Groenendael R, Leijte GP, Kox M, Pickkers P . Proenkephalin Compared to Conventional Methods to Assess Kidney Function in Critically Ill Sepsis Patients . Shock . 54 . 3 . 308–314 . September 2020 . 31977957 . 7458088 . 10.1097/SHK.0000000000001510 .

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