Human brain cathepsin H as a neuropeptide and bradykinin metabolizing enzyme.
Highly purified human brain cathepsin H (EC 3.4.22.16) was used to study its involvement in degradation of different brain peptides. Its action was determined to be selective. On Leu-enkephalin, dynorphin (1-6), dynorphin (1-13), alpha-neoendorphin, and Lys-bradykinin, it showed a preferential aminopeptidase activity by cleaving off hydrophobic or basic amino acids. It showed no aminopeptidase activity on bradykinin, which has Pro adjacent to its N-terminal amino acid, on neurotensin with blocked N-terminal amino acid, or on dermorphin with second amino acid D-alanine. After prolonged incubation, cathepsin H acted as an endopeptidase. Dermorphin and dynorphin (1-13) were cleaved at bonds with Phe in the P2 position, while dynorphin (1-6), alpha-neoendorphin, bradykinin and Lys-bradykinin were cleaved at bonds with Gly in the P2 position. Further on, it was shown that human brain cathepsin H activity could be controlled in vivo by cystatin C in its full-length form or its [delta1-10] variant, already known to be co-localized in astrocytes, since the Ki values for the inhibition are in the 10(-10) M range.
Brguljan
Pika Mesko
PM
Department of Biochemistry and Molecular Biology, Jozef Stefan Institute, Jamova 39, Ljubljana 1000, Slovenia.
Turk
Vito
V
Nina
Cimerman
C
Brzin
Joze
J
Krizaj
Igor
I
Popovic
Tatjana
T
D001920:Bradykinin / Q000378:metabolism*; D001921:Brain / Q000201:enzymology*; D056655:Cathepsin H; D002403:Cathepsins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D055316:Cystatin C; D015891:Cystatins / Q000494:pharmacology; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D009479:Neuropeptides / Q000378:metabolism*
C525030:CST3 protein, human; D055316:Cystatin C; D015891:Cystatins; D009479:Neuropeptides; D002403:Cathepsins; D003546:Cysteine Endopeptidases; C534126:CTSH protein, human; D056655:Cathepsin H; D001920:Bradykinin