TY - JOUR
T1 - Degradation of dynorphin-related peptides by the puromyein-sensitive aminopeptidase and aminopeptidase M
AU - Safavi, Afshin
AU - Hersh, Louis B.
PY - 1995/7
Y1 - 1995/7
N2 - The degradation of dynorphin-related peptides by the puromycin-sensitive aminopeptidase and aminopeptidase M was examined using these peptides as alternate substrate inhibitors. Ki determinations showed that both aminopeptidases exhibit a higher affinity for longer dynorphin-related peptides, i.e., Ki for dynorphin A-17 = 23-30 nM with the Ki increasing to 25-50 μM for the enkephalin pentapeptides. Binding appears dependent not only on peptide length, but also on its sequence. With aminopeptidase M, as the peptide size increases from five to 10 amino acids, kcat remains relatively constant; however, as the peptide size increases beyond a decapeptide, kcat decreases significantly. With the puromycin-sensitive aminopeptidase, similar results were obtained except that kcat was greatest for the pentapeptide. Thus, if one considers kcat/Km as the relevant kinetic constant for estimating in vivo peptide hydrolysis, these results are consistent with the involvement of aminopeptidase M and the puromycin-sensitive aminopeptidase in the degradation of extended dynorphin-related peptides.
AB - The degradation of dynorphin-related peptides by the puromycin-sensitive aminopeptidase and aminopeptidase M was examined using these peptides as alternate substrate inhibitors. Ki determinations showed that both aminopeptidases exhibit a higher affinity for longer dynorphin-related peptides, i.e., Ki for dynorphin A-17 = 23-30 nM with the Ki increasing to 25-50 μM for the enkephalin pentapeptides. Binding appears dependent not only on peptide length, but also on its sequence. With aminopeptidase M, as the peptide size increases from five to 10 amino acids, kcat remains relatively constant; however, as the peptide size increases beyond a decapeptide, kcat decreases significantly. With the puromycin-sensitive aminopeptidase, similar results were obtained except that kcat was greatest for the pentapeptide. Thus, if one considers kcat/Km as the relevant kinetic constant for estimating in vivo peptide hydrolysis, these results are consistent with the involvement of aminopeptidase M and the puromycin-sensitive aminopeptidase in the degradation of extended dynorphin-related peptides.
KW - Aminopeptidase
KW - Des-tyrosyl dynorphins
KW - In vivo metabolism
UR - http://www.scopus.com/inward/record.url?scp=0029046205&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029046205&partnerID=8YFLogxK
M3 - Article
C2 - 7790884
AN - SCOPUS:0029046205
SN - 0022-3042
VL - 65
SP - 389
EP - 395
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
IS - 1
ER -