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Peptide alpha-amidation activity in human plasma: relationship to gastrin processing

M Kapuscinski1, M Green, S N Sinha

  • 1Department of Surgery, University of Melbourne, Austin Hospital, Victoria, Australia.

Clinical Endocrinology
|July 1, 1993
PubMed
Summary

Plasma peptidylglycine alpha-amidating mono-oxygenase (PAM) activity correlates with gastrin levels in certain conditions, but does not appear to be involved in post-secretory gastrin amidation. Gastrin is likely amidated at its synthesis site.

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Isolation, identification and biological activity of gastrin-releasing peptide 1-46 (oGRP 1-46), the primary GRP gene-derived peptide product of the pregnant ovine endometrium.

Peptides·2009

Area of Science:

  • Biochemistry
  • Endocrinology
  • Molecular Biology

Background:

  • C-terminal amidation is crucial for the bioactivation of peptides like gastrin.
  • Peptidylglycine alpha-amidating mono-oxygenase (PAM) catalyzes this amidation reaction.
  • The role of circulating PAM in post-secretory gastrin processing remains unclear.

Purpose of the Study:

  • To investigate the relationship between circulating PAM activity and plasma concentrations of glycine-extended and amidated gastrins.
  • To determine if circulating PAM reflects gastrin secretory activity or participates in post-secretory processing.

Main Methods:

  • Measured plasma PAM activity, amidated gastrin (G-NH2), and glycine-extended gastrin (G-gly) in various subject groups.
  • Included healthy individuals, families with multiple endocrine neoplasia type 1 (MEN-1), and patients with hypergastrinaemic atrophic gastritis.

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Main Results:

  • Elevated plasma PAM activity was observed in MEN-1 patients with hypergastrinaemia, suggesting co-secretion of gastrin and PAM.
  • PAM activity was not a reliable tumor marker for gastrinoma.
  • Hypergastrinaemia from non-tumoral sources was linked to lower PAM activity, potentially indicating secretion of already amidated gastrin.
  • No correlation was found between plasma PAM activity and the ratio of amidated to non-amidated gastrin.

Conclusions:

  • Gastrin amidation likely occurs at the site of synthesis.
  • Elevated plasma PAM activity in hypergastrinaemia is primarily associated with gastrin originating from tumor sources.