A placental enzyme degraded met-enkephalin and leu-enkephalin completely into amino acids, with larger opioid peptides being broken down more slowly.
Complete degradationMet-enkephalin and leu-enkephalin broken into all 5 amino acids by one enzyme
What the researchers 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).
Why it 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.
How the study worked
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).
What this study cannot 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.
How to read the evidence
Preliminary in-vitro study using purified enzyme — clear results but isolated conditions.
When this study was published
Published in 1988 — relevant to ongoing challenges in peptide drug delivery.
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.
Questions still open
- Can enzyme inhibitors protect therapeutic peptides from degradation?
- Does this enzyme affect fetal exposure to maternal opioid peptides?
Common questions
Why do peptide drugs break down so easily?
What is aminopeptidase M?
Read the original research
In vitro degradation of opioid peptides by human placental aminopeptidase M.
Experimental and clinical endocrinology, 92(2), 235-7
Citation
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.