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Isolation and structure of pro-methionine-enkephalin: Potential enkephalin precursor from porcine hypothalamus
W Y Huang1, R C Chang, A J Kastin
1Endocrine and Polypeptide Laboratory, Veterans Administration Medical Center, New Orleans, Louisiana 70146.
Abstract:
A hexapeptide that we have named pro-methionine-enkephalin has been isolated from acid extracts of porcine hypothalami and found to have the amino acid sequence H-Tyr-Gly-Gly-Phe-Met(O)-Arg-OH. This peptide is not a fragment of either porcine beta-lipotropin or beta-endorphin, which suggests that it could be a precursor of [Met]enkephalin in the brain by a pathway differing from the one usually postulated. The existence of still larger precursors of [Met]enkephalin, perhaps related to the recently reported alpha-neo-endorphin, is strongly implied by these studies. Synthetic H-Tyr-Gly-Gly-Phe-Met-Arg-OH exhibited low, but significant, opiate activity in vitro.
Insights
Researchers discovered a novel hexapeptide, pro-methionine-enkephalin, in pig hypothalami. This peptide may represent a new precursor pathway for [Met]enkephalin in the brain.
Area of Science:
- Neuroscience
- Biochemistry
- Endocrinology
Background:
- The biosynthesis of endogenous opioids, such as [Met]enkephalin, is complex.
- Existing models suggest precursors like pro-opiomelanocortin (POMC) and proenkephalin (PE).
- The precise pathways for all opioid peptide generation remain under investigation.
Purpose of the Study:
- To isolate and characterize novel peptides from porcine hypothalami.
- To investigate potential new precursors of [Met]enkephalin.
- To determine the opioid activity of the newly identified peptide.
Main Methods:
- Acid extraction of porcine hypothalami.
- Peptide isolation and purification.
- Amino acid sequencing of the isolated peptide.
- In vitro opiate activity assays.
Main Results:
- Isolation of a hexapeptide, pro-methionine-enkephalin (H-Tyr-Gly-Gly-Phe-Met(O)-Arg-OH).
- The peptide is not a fragment of beta-lipotropin or beta-endorphin.
- Synthetic pro-methionine-enkephalin demonstrated low but significant in vitro opiate activity.
- Findings imply larger, uncharacterized precursors of [Met]enkephalin.
Conclusions:
- Pro-methionine-enkephalin represents a potential novel precursor for [Met]enkephalin.
- This suggests an alternative biosynthetic pathway for [Met]enkephalin.
- The existence of larger opioid peptide precursors is strongly indicated.
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