Specificity of action of human brain alanyl aminopeptidase on Leu-enkephalin and dynorphin-related peptides.
The major cystosolic aminopeptidase (alanylaminopeptidase) was purified to homogeneity from human cerebral cortex and the specificity of its actions on a series of Leu-enkephalin-related peptides of increasing chain length was determined. In each case, only the N-terminal Tyr-Gly bond was hydrolysed. Kinetic analysis of the data revealed that the specificity constant (kcat/Km;s-1M-1) falls with increasing chain length from a maximum of 13.6 x 10(4) for Leu-enkephalin (5 residues) to 5.8 x 10(2) for dynorphin (1-13). Dynorphin 1-17, while not being degraded itself acted as a competitive inhibitor (Ki = 2.7 microM) of the degradation of smaller peptides. Beta-endorphin was not hydrolysed by analylaminopeptidase, nor did it act as an inhibitor of the enzyme.
Gibson
A M
AM
MRC Neurochemical Pathology Unit, Newcastle upon Tyne, UK.
McDermott
J R
JR
Lauffart
B
B
Mantle
D
D
D000626:Aminopeptidases / Q000302:isolation & purification / Q000378:metabolism*; D018826:CD13 Antigens; D002540:Cerebral Cortex / Q000201:enzymology*; D004399:Dynorphins / Q000378:metabolism*; D004743:Enkephalin, Leucine / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D010446:Peptide Fragments / Q000378:metabolism*; D013379:Substrate Specificity
D010446:Peptide Fragments; D004743:Enkephalin, Leucine; D004399:Dynorphins; D000626:Aminopeptidases; D018826:CD13 Antigens