The combined action of two enzymes in human serum can mimic the activity of cathepsin B.
Synthetic substrates are often used to measure the activity of proteolytic enzymes. We have investigated the activities which cleave synthetic substrates such as alpha-N-benzyloxycarbonyl-Arg-Arg-beta-naphthylamide, for which the lysosomal proteinase cathepsin B has a high affinity, in sera from normal individuals, pregnant women and patients with breast cancer. As reported by other workers, activities against these substrates were elevated during pregnancy. Naphthylamine release, however, was shown to be the result of the combined action of two enzymes. The substrate is first cleaved by an endopeptidase to yield alpha-N-benzyloxycarbonyl-Arg and the aminopeptidase substrate Arg-beta-naphthylamide, which is then cleaved by serum aminopeptidases, particularly oxytocinase. A similar mechanism of cleavage was also found in the sera of breast cancer patients, where the endopeptidase catalyzing the first reaction was characterized as plasma kallikrein and the second reaction was carried out by serum leucine aminopeptidase. In no serum sample was there evidence for true cathepsin B activity.
D000626:Aminopeptidases / Q000097:blood*; D001587:Benzoylarginine-2-Naphthylamide / Q000031:analogs & derivatives / Q000378:metabolism; D001943:Breast Neoplasms / Q000097:blood*; D002401:Cathepsin B; D002403:Cathepsins / Q000097:blood*; D010122:Cystinyl Aminopeptidase / Q000097:blood; D010450:Endopeptidases / Q000097:blood*; D005260:Female; D006801:Humans; D007610:Kallikreins / Q000097:blood; D007931:Leucyl Aminopeptidase / Q000097:blood; D011247:Pregnancy; D013379:Substrate Specificity
D001587:Benzoylarginine-2-Naphthylamide; C028469:N-benzyloxycarbonylarginyl-L-arginine-2-naphthylamide; D002403:Cathepsins; D010450:Endopeptidases; D000626:Aminopeptidases; D007931:Leucyl Aminopeptidase; D010122:Cystinyl Aminopeptidase; D007610:Kallikreins; D002401:Cathepsin B