PMID- 8102327 OWN - NLM STAT- MEDLINE DCOM- 19930913 LR - 20190813 IS - 0300-0664 (Print) IS - 0300-0664 (Linking) VI - 39 IP - 1 DP - 1993 Jul TI - Peptide alpha-amidation activity in human plasma: relationship to gastrin processing. PG - 51-8 AB - OBJECTIVE AND DESIGN: C-terminal amidation is an essential processing step towards bioactivation of many peptides including gastrin. This reaction is catalysed by peptidylglycine alpha-amidating mono-oxygenase (PAM, EC 1.14.17.3) which converts the glycine extended precursors on their carboxyl termini to the des-glycine amidated peptide products. In the case of gastrin, most of the amidation is thought to occur in the antrum. However substantial quantities of glycine extended gastrin and PAM are present in plasma. It is unclear whether circulating PAM reflects the secretory activity of the gastrin secreting cell or whether PAM is involved in the postsecretory processing of gastrin. The aim of the present study was to relate the circulating amidation activity to the plasma concentrations of glycine extended and amidated gastrins. PATIENTS AND MEASUREMENTS: Plasma PAM, gastrin-amide and gastrin-gly were measured in subjects with different gastrin secretory status: healthy subjects basally and following a meal, members of families with multiple endocrine neoplasia type 1 (MEN-1) with normal and high plasma gastrin, and patients with hypergastrinaemic atrophic gastritis. RESULTS: Patients with MEN-1 and hypergastrinaemia tended to have a higher plasma PAM activity than MEN-1 subjects with normal circulating G-NH2 indicating a cosecretion of hormone and PAM. However in contradistinction to patients with medullary thyroid carcinoma, PAM activity does not appear to be a useful tumour marker of gastrinoma. Hypergastrinaemia from a non-tumour source (hypergastrinaemic non-atrophic gastritis) was associated with a lower plasma PAM activity than in normal subjects and may reflect the secretion of a greater proportion of already amidated gastrin. In general, there was no relationship between plasma PAM activity and the ratio of amidated to non-amidated gastrin suggesting that circulating PAM was not involved in the amidation of gastrin. Feeding increased circulating gastrin but had no effect on plasma PAM activity. CONCLUSION: The results support the view that gastrin is amidated at the site of its synthesis and that hypergastrinaemia is associated with elevated plasma amidating enzyme activity only when the gastrin originates from tumour sources. FAU - Kapuscinski, M AU - Kapuscinski M AD - Department of Surgery, University of Melbourne, Austin Hospital, Victoria, Australia. FAU - Green, M AU - Green M FAU - Sinha, S N AU - Sinha SN FAU - Shepherd, J J AU - Shepherd JJ FAU - Shulkes, A AU - Shulkes A LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Clin Endocrinol (Oxf) JT - Clinical endocrinology JID - 0346653 RN - 0 (Gastrins) RN - 0 (Multienzyme Complexes) RN - 789U1901C5 (Copper) RN - EC 1.- (Mixed Function Oxygenases) RN - EC 1.14.17.3 (peptidylglycine monooxygenase) RN - PQ6CK8PD0R (Ascorbic Acid) SB - IM MH - Anemia, Pernicious/blood MH - Ascorbic Acid/metabolism MH - Copper/metabolism MH - Eating/physiology MH - Enzyme Activation/physiology MH - Freezing MH - Gastrins/blood/*metabolism MH - Humans MH - Mixed Function Oxygenases/*blood/metabolism MH - *Multienzyme Complexes MH - Multiple Endocrine Neoplasia/blood MH - Vitamin B 12 Deficiency/blood EDAT- 1993/07/01 00:00 MHDA- 1993/07/01 00:01 CRDT- 1993/07/01 00:00 PHST- 1993/07/01 00:00 [pubmed] PHST- 1993/07/01 00:01 [medline] PHST- 1993/07/01 00:00 [entrez] AID - 10.1111/j.1365-2265.1993.tb01750.x [doi] PST - ppublish SO - Clin Endocrinol (Oxf). 1993 Jul;39(1):51-8. doi: 10.1111/j.1365-2265.1993.tb01750.x.