In vitro and in vivo degradation of human gastrin by endopeptidase 24.11.
The degradation of human unsulfated heptadecapeptide gastrin (G-17) by human kidney endopeptidase 24.11 has been studied in vitro, and some of the products of degradation have been identified in plasma after in vivo infusion of G-17. The enzyme cleaved G-17 at four peptide bonds: Trp4Leu5, Ala11Tyr12, Gly13Trp14, and Asp16Phe17. The cleavage at Gly-Trp was rapid and 1-13 G-17 was an important intermediate. All the products of cleavage of synthetic 1-13 G-17 were also found after degradation of intact G-17. When normal human volunteers received infusions of G-17, there appeared in their blood peptides with the properties of 1-11, 1-13, 1-16, and 5-17 G-17 on the basis of immunochemical and high-performance liquid chromatographic properties. These observations provide evidence that endopeptidase 24.11 is involved in gastrin metabolism in humans, and may be responsible for the generation of G-17 fragments in the peripheral circulation.
Deschodt-Lanckman
M
M
Laboratoire Pluridisciplinaire de Recherche Expérimentale Biomedicale, Faculté de Médecine, Campus Erasme, U.L.B., Brussels, Belgium.
Pauwels
S
S
Najdovski
T
T
Dimaline
R
R
Dockray
G J
GJ
D005755:Gastrins / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008666:Metalloendopeptidases / Q000494:pharmacology*; D015260:Neprilysin
D005755:Gastrins; C013550:gastrin 17; D008666:Metalloendopeptidases; D015260:Neprilysin