[Proteolytic processing by dipeptidyl aminopeptidase IV generates receptor selectivity for peptide YY (PYY)].
Two receptor subtypes, Y1 and Y2, are known to mediate PYY biological activity. PYY 1-36 binds to Y1 and Y2 receptors with equal affinity, whereas the second endogenous form of PYY, PYY 3-36, selectively binds to Y2 receptors. Dipeptidyl cleavage thus transforms an unselective Y agonist into a highly selective Y2 agonist, PYY 3-36. The enzyme responsible for this processing is unknown. Since PYY has a proline in the penultimate position it is protected from the attack of most unspecific exopeptidases. Only a few exopeptidases are theoretically capable of generating PYY 3-36 from PYY 1-36. Of the enzymes tested only the dipeptidyl aminopeptidase IV (DPP IV, E.C. 3.4.14.5) cleaved Tyr-Pro from PYY 1-36 with high activity. Since DPP IV is found on the endothelial surface and brush border membranes it can be considered a candidate enzyme for generating PYY 3-36 in vivo, thereby regulating the ratio of Y1/Y2 receptor stimulation by PYY.
Grandt
D
D
Medizinische Klinik und Poliklinik, Abteilung für Gastroenterologie, Klinikum der Universität, Essen.
Dahms
P
P
Schimiczek
M
M
Eysselein
V E
VE
Reeve
J R
JR
Mentlein
R
R
D018819:Dipeptidyl Peptidase 4; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000502:physiology*; D006801:Humans; D010446:Peptide Fragments / Q000378:metabolism*; D019894:Peptide YY; D010455:Peptides / Q000378:metabolism*; D017476:Receptors, Neuropeptide Y / Q000378:metabolism*
D010446:Peptide Fragments; D010455:Peptides; D017476:Receptors, Neuropeptide Y; D019894:Peptide YY; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D018819:Dipeptidyl Peptidase 4
Proteolytisches Processing durch Dipeptidyl-Aminopeptidase IV generiert Rezeptorselektivität für Peptid YY (PYY).