Proenkephalin (PENK)

Proenkephalin (PENK) is a peptide hormone precursor that is proteolytically cleaved to produce several biologically active opioid neuropeptides, most notably Met-enkephalin and Leu-enkephalin[1][2][3]. These peptides are stored in synaptic vesicles and released to act on opioid receptors, broadly modulating pain perception, stress responses, and neuronal transmission. Beyond neuronal functions, PENK is expressed in multiple tissues, influencing immune response, cell survival, and organ regeneration (especially in kidneys)[2][3]. Aberrant methylation or downregulation of PENK is implicated in tumor progression, and its fragments in circulation serve as biomarkers of kidney function and neurological disease severity. Drugs influencing PENK pathways include antagonists for research and demethylating agents for cancers with silenced PENK. Safety considerations center around opioid-related pathways, addiction risk, and systemic effects across multiple organs.

Other names

Proenkephalin-ASynenkephalinMet-enkephalinPENK(114-133)PENK(143-183)Met-enkephalin-Arg-Gly-LeuLeu-enkephalinPENK(237-258)Met-enkephalin-Arg-PheOGF (Opioid growth factor)preproenkephalinPEPENK-Aenkephalin Apeptide F

Activation or inhibition of opioid receptors (mu- and delta-opioid receptors) by enkephalin peptides. Tumor suppression via induction of apoptosis and cell migration inhibition (modulation of PI3K/Akt pathway). Regulation of kidney regeneration by modulating H2O2 production and feedback mechanisms. Analgesia via increased endogenous Met-enkephalin (upregulation in Nav1.7 deletion).