TY - JOUR
T1 - Angiotensin I conversion by human and rat chymotryptic proteinases
AU - Wintroub, B. U.
AU - Schechter, N. B.
AU - Lazarus, G. S.
AU - Kaempfer, C. E.
AU - Schwartz, L. B.
N1 - Funding Information:
Manuscript received May 22, 1984: accepted for publication July 13, J984. This work was supported by the Veterans Administration, National Institutes of Health Grants AI 20487, AM :)2070, and 2:1888. Reprint requests to: Bruce U. Wint.roub, M.D., Derm atology Service ( 190), Veterans Administration Medical Center, 4150 Clement Street, San Francisco. California 94121. Abbrev iations: ACE: angiotensin-converting enzyme BTEE: benzoyl-L-tyrosine ethyl ester bz-arg-pro-phe-p-NA: benzoyl-r.-arginine-L-proline-L-phenylala-nine-p-NA CM: carboxymethyl DFP: diisopropyl fluorophosphate DTME: n-tryptophan methyl ester 1-IPLC: high-performance liquid chromatography p-NA: paranitroanilide suc-arg-pro-tyr-p-N A: succi nyi-L-arginine· L-proline-L-tyrosine-p-NA
PY - 1984
Y1 - 1984
N2 - Human skin chymotrypsin-like proteinase, human neutrophil cathepsin G, rat mast cell chymase, and rat salivary gland tonin are cell-derived serine proteinases of similar size with specificity for amino acids of aromatic residues. Each enzyme was examined for its ability to convert angiotensin I to angiotensin I and converted angiotensin I to angiotensin II and to cleave a panel of synthetic substrates. Skin chymotryptic proteinase, cathepsin G, and tonin cleaved the phe8-his9 bond of angiotensin II without further degradation. In contrast, chymase formed relatively small amounts of angiotensin II because it preferentially cleaved the tyr4-ile5 bond of angiotensin I. The rank order of angiotensin I converting activity was skin chymotryptic proteinase > tonin > cathepsin G > chymase. The K(m) and K(cat) for angiotensin I conversion by the human skin enzyme were 6.6 x 10-5 M and 50 s-1, respectively. The angiotensin I converting activity of human skin chymotryptic proteinase is equal to or greater than the peptidyl dicarboxypeptidase angiotensin-converting enzyme. Substrate specificities of each enzyme were further distinguished by use of benzoyl-L-tyrosine ethyl ester. A limited immunologic characterization of each enzyme was performed with monospecific goat antiserum to cathepsin G and chymase by Ochterlony gel diffusion. Each antiserum gave a precipitin line against its respective immunogen without evidence of cross-reactivity against the other enzymes. Human skin chymotryptic proteinase, cathepsin G, and tonin provide unique pathways for the generation of angiotensin II in tissue and may be of significance in regulation of biologic processes of the tissue microenvironment. The kinetic constants of the human skin chymotryptic proteinase for angiotensin I conversion, are consistent with the potential to carry out a reaction of physiologic importance.
AB - Human skin chymotrypsin-like proteinase, human neutrophil cathepsin G, rat mast cell chymase, and rat salivary gland tonin are cell-derived serine proteinases of similar size with specificity for amino acids of aromatic residues. Each enzyme was examined for its ability to convert angiotensin I to angiotensin I and converted angiotensin I to angiotensin II and to cleave a panel of synthetic substrates. Skin chymotryptic proteinase, cathepsin G, and tonin cleaved the phe8-his9 bond of angiotensin II without further degradation. In contrast, chymase formed relatively small amounts of angiotensin II because it preferentially cleaved the tyr4-ile5 bond of angiotensin I. The rank order of angiotensin I converting activity was skin chymotryptic proteinase > tonin > cathepsin G > chymase. The K(m) and K(cat) for angiotensin I conversion by the human skin enzyme were 6.6 x 10-5 M and 50 s-1, respectively. The angiotensin I converting activity of human skin chymotryptic proteinase is equal to or greater than the peptidyl dicarboxypeptidase angiotensin-converting enzyme. Substrate specificities of each enzyme were further distinguished by use of benzoyl-L-tyrosine ethyl ester. A limited immunologic characterization of each enzyme was performed with monospecific goat antiserum to cathepsin G and chymase by Ochterlony gel diffusion. Each antiserum gave a precipitin line against its respective immunogen without evidence of cross-reactivity against the other enzymes. Human skin chymotryptic proteinase, cathepsin G, and tonin provide unique pathways for the generation of angiotensin II in tissue and may be of significance in regulation of biologic processes of the tissue microenvironment. The kinetic constants of the human skin chymotryptic proteinase for angiotensin I conversion, are consistent with the potential to carry out a reaction of physiologic importance.
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U2 - 10.1111/1523-1747.ep12264144
DO - 10.1111/1523-1747.ep12264144
M3 - Article
C2 - 6092480
AN - SCOPUS:0021137396
SN - 0022-202X
VL - 83
SP - 336
EP - 339
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 5
ER -