Human Placental Enzyme Rapidly Breaks Down Pain-Killing Opioid Peptides
A placental enzyme degraded met-enkephalin and leu-enkephalin completely into amino acids, with larger opioid peptides being broken down more slowly.
Quick Facts
What This Study Found
Human placental aminopeptidase M completely degraded Met-enkephalin and Leu-enkephalin into their five constituent amino acids. The degradation rate was measured by tracking tyrosine release.
The degradation speed ranked: Met-enkephalin (fastest) > Leu-enkephalin > beta-neoendorphin > dynorphin > beta-endorphin (slowest).
Smaller, simpler peptides were degraded faster than larger, more complex ones. Met-enkephalin (5 amino acids) was destroyed faster than beta-endorphin (31 amino acids).
Key Numbers
How They Did This
Purified aminopeptidase M from human placenta was incubated with each opioid peptide. Degradation was measured by HPLC detection of released amino acids, specifically tyrosine (the first amino acid in all opioid peptides).
Why This Research Matters
Understanding how fast the body breaks down opioid peptides explains why some last longer than others. This information matters for designing peptide drugs that resist degradation and for understanding why injected peptides have limited duration of action.
The Bigger Picture
Peptide degradation by tissue enzymes is the main barrier to oral peptide drug delivery. Understanding which enzymes break down which peptides informs the design of more stable therapeutic peptides.
What This Study Doesn't Tell Us
In vitro study with a single purified enzyme. In the body, multiple enzymes work together. Placental enzyme may behave differently from enzymes in the brain or blood. Did not test modified or synthetic opioid peptides.
Questions This Raises
- ?Can enzyme inhibitors protect therapeutic peptides from degradation?
- ?Does this enzyme affect fetal exposure to maternal opioid peptides?
Trust & Context
- Key Stat:
- Complete degradation Met-enkephalin and leu-enkephalin broken into all 5 amino acids by one enzyme
- Evidence Grade:
- Preliminary in-vitro study using purified enzyme — clear results but isolated conditions.
- Study Age:
- Published in 1988 — relevant to ongoing challenges in peptide drug delivery.
- Original Title:
- In vitro degradation of opioid peptides by human placental aminopeptidase M.
- Published In:
- Experimental and clinical endocrinology, 92(2), 235-7 (1988)
- Authors:
- Furuhashi, M, Mizutani, S, Kurauchi, O, Kasugai, M, Narita, O, Tomoda, Y
- Database ID:
- RPEP-00072
Evidence Hierarchy
Frequently Asked Questions
Why do peptide drugs break down so easily?
The body has many enzymes designed to recycle peptides. These enzymes rapidly cut peptides into amino acids, which is why most peptide drugs cannot be taken orally and must be injected.
What is aminopeptidase M?
An enzyme that clips amino acids off the front end of peptides. It is found in many tissues including the placenta, gut, and kidneys, and is a major barrier to peptide drug delivery.
Read More on RethinkPeptides
Cite This Study
https://rethinkpeptides.com/research/RPEP-00072APA
Furuhashi, M; Mizutani, S; Kurauchi, O; Kasugai, M; Narita, O; Tomoda, Y. (1988). In vitro degradation of opioid peptides by human placental aminopeptidase M.. Experimental and clinical endocrinology, 92(2), 235-7.
MLA
Furuhashi, M, et al. "In vitro degradation of opioid peptides by human placental aminopeptidase M.." Experimental and clinical endocrinology, 1988.
RethinkPeptides
RethinkPeptides Research Database. "In vitro degradation of opioid peptides by human placental a..." RPEP-00072. Retrieved from https://rethinkpeptides.com/research/furuhashi-1988-in-vitro-degradation-of
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.