Human dipeptidyl peptidase III acts as a post-proline-cleaving enzyme on endomorphins.
Dipeptidyl peptidase III (DPP III) is a zinc exopeptidase with an implied role in the mammalian pain-modulatory system owing to its high affinity for enkephalins and localisation in the superficial laminae of the spinal cord dorsal horn. Our study revealed that this human enzyme hydrolyses opioid peptides belonging to three new groups, endomorphins, hemorphins and exorphins. The enzymatic hydrolysis products of endomorphin-1 were separated and quantified by capillary electrophoresis and the kinetic parameters were determined for human DPP III and rat DPP IV. Both peptidases cleave endomorphin-1 at comparable rates, with liberation of the N-terminal Tyr-Pro. This is the first evidence of DPP III acting as an endomorphin-cleaving enzyme.
Barsun
Marina
M
PLIVA Research and Development Ltd., Prilaz baruna Filipovića 25, 10000 Zagreb, Croatia.
Jajcanin
Nina
N
Vukelić
Bojana
B
Spoljarić
Jasminka
J
Abramić
Marija
M
D000626:Aminopeptidases / Q000378:metabolism; D000818:Animals; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000378:metabolism*; D006801:Humans; D009842:Oligopeptides / Q000378:metabolism*; D011392:Proline; D000085822:Prolyl Oligopeptidases; D051381:Rats; D012697:Serine Endopeptidases / Q000378:metabolism*
D009842:Oligopeptides; C105293:endomorphin 1; D011392:Proline; D000626:Aminopeptidases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C100152:dipeptidyl peptidase III; D012697:Serine Endopeptidases; C000705287:PREPL protein, human; D000085822:Prolyl Oligopeptidases