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| Names | |
|---|---|
| IUPAC name (2S)-2-[[(2S)-2-[[2-[[2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]acetyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-4-methylsulfanylbutanoic acid | |
| Other names [Met]enkephalin; [Met5]enkephalin;L-Tyrosylglycylglycyl-L-phenylalanyl-L-methionine | |
| Identifiers | |
3D model (JSmol) | |
| ChEBI | |
| ChEMBL | |
| ChemSpider |
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| ECHA InfoCard | 100.055.741 |
| EC Number |
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| KEGG |
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| MeSH | Enkephalin,+Methionine |
| UNII | |
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| Properties | |
| C27H35N5O7S | |
| Molar mass | 573.67 g·mol−1 |
| logP | 0.607 |
| Acidity (pKa) | 3.234 |
| Basicity (pKb) | 10.763 |
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). | |
Met-enkephalin, also known asmetenkefalin (INN), sometimes referred to asopioid growth factor (OGF),[1] is anaturally occurring,endogenousopioid peptide that hasopioid effects of a relatively short duration. It is one of the two forms ofenkephalin, the other beingleu-enkephalin. The enkephalins are considered to be the primary endogenous ligands of theδ-opioid receptor, due to their highpotency andselectivity for the site over the otherendogenous opioids.[2]
Met-enkephalin was discovered and characterized byJohn Hughes,Hans Kosterlitz,et al. in 1975 after a search for endogenous ligands of the opioid receptors.[3]
Met-enkephalin is apentapeptide with theamino acid sequence Tyr-Gly-Gly-Phe-Met. Thetyrosineresidue at position 1 is thought to beanalogous to the 3-hydroxylgroup onmorphine.[citation needed]
Met-enkephalin is found mainly in theadrenal medulla and throughout thecentral nervous system (CNS), including in thestriatum,cerebral cortex,olfactory tubercle,hippocampus,septum,thalamus, andperiaqueductal gray, as well as thedorsal horn of thespinal cord.[2] It is also present in the periphery, notably in someprimary afferent fibers thatinnervate thepelvic viscera.[2]
Met-enkephalin issynthesized fromproenkephalin viaproteolyticcleavage[4] in twometabolic steps. Proenkephalin A is first reduced by either one of twotrypsin-likeendopeptidaseenzymes,prohormone convertase 1 (PC1) orprohormone convertase 2 (PC2); then, the resultingintermediates are further reduced by the enzymecarboxypeptidase E (CPE; previously known as enkephalin convertase (EC)).[5][6] Proenkephalin A contains four sequences of met-enkephalin (at the following positions: 100–104; 107–111; 136–140; 210–214), and as a result, its cleavage generates four copies of met-enkephalin peptides at once.[4] In addition, anabolism of proenkephalin A results in the production of one copy each of twoC-terminal-extended met-enkephalinderivatives, theheptapeptide met-enkephalin-arg-phe (261–267), and theoctapeptide met-enkephalin-arg-gly-leu (186–193),[4] though whether they affect the opioid receptors in a similar manner as met-enkephalin is not entirely clear.[7]
Met- and leu-enkephalin are metabolized by a variety of different enzymes, includingaminopeptidase N (APN),[8]neutral endopeptidase (NEP),[8]dipeptidyl peptidase 3 (DPP3),[8]carboxypeptidase A6 (CPA6),[9] andangiotensin-converting enzyme (ACE).[10] These enzymes are sometimes referred to asenkephalinases.
Met-enkephalin is apotentagonist of theδ-opioid receptor, and to a lesser extent theμ-opioid receptor, with little to no effect on theκ-opioid receptor. It is through these receptors that met-enkephalin produces its opioid effects, such asanalgesia andantidepressant-like effects.
It is also the endogenousligand of theopioid growth factor receptor (OGFR; formerly known as the ζ-opioid receptor), which plays a role in the regulation of tissue growth and regeneration; hence why met-enkephalin is sometimes called OGF instead.
Met-enkephalin has lowbioavailability, is rapidlymetabolized, and has a very shorthalf-life (minutes).[3][11] These properties are considered undesirable in pharmaceuticals as large doses would need to be administered multiple times an hour to maintain a therapeutically relevant effect, making it unlikely that met-enkephalin will ever be used as a medicine.
[D-Ala2]-Met-enkephalinamide (DALA), is a synthetic enkephalin analog which is not susceptible to degradation by brain enzymes and at low doses (5 to 10 micrograms) caused profound, long-lasting, morphine-like analgesia when microinjected into a rat’s brain.[12]
