Hemorphins: substrates and/or inhibitors of dipeptidyl peptidase IV. Hemorphins N-terminus sequence influence on the interaction between hemorphins and DPPIV.
Hemorphins are endogenous peptides belonging to the family of "atypical" opioid peptides released from sequentially hydrolyzed hemoglobin. In this paper, we report an inhibitory effect of these peptides on dipeptidyl peptidase IV (DPPIV) activity, known to be involved in regulatory functions such as the activation or inactivation of peptides. The structure activity research revealed that hemorphins N-terminus sequence influences nature of the interaction between hemorphins and DPPIV. Kinetic studies conducted with purified DPPIV demonstrated that hemorphin-7 (H7) constitutes a good substrate (K(cat)/K(m) of 137 mM(-1) s(-1)) for this enzyme but could also act as a selective competitive inhibitor by substrate binding site competition. These blood-derived peptides could represent endogenous regulators of this enzyme activity.
Laboratoire de Génie Protéique et Cellulaire, EA3169, Bâtiment Marie-Curie, avenue Michel-Crépeau, 17042 La Rochelle cedex 1, France.
M
M
Cohen
I
I
Fruitier-Arnaudin
J M
JM
Piot
D000818:Animals; D018819:Dipeptidyl Peptidase 4 / Q000737:chemistry / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000378:metabolism / Q000494:pharmacology; D006454:Hemoglobins / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D007668:Kidney / Q000201:enzymology*; D008297:Male; D008861:Microsomes / Q000201:enzymology*; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D013379:Substrate Specificity
D004791:Enzyme Inhibitors; D006454:Hemoglobins; D010446:Peptide Fragments; D018819:Dipeptidyl Peptidase 4