The recognition site for hepatic clearance of plasma kallikrein is on its heavy chain and is latent on prokallikrein.
We partially purified the glycoproteins prokallikrein and kallikrein from rat plasma. The purification of rat plasma kallikrein may result in two forms: an intact form (alpha, M(r) 84-87 kDa) and a partially degraded form (beta, M(r) 46-51 kDa). The alpha-form is composed of a heavy chain (M(r) 50 kDa) and a light chain (M(r) 34-37 kDa) linked by a disulfide bond. The catalytic site is found on the light chain. The beta-form has a partially degraded heavy chain (M(r) 28 kDa). Using a preparation of exsanguinated and perfused rat liver, we verified that rat plasma prokallikrein is not activated by the liver and that neither the proenzyme nor the light chain is removed by the organ. Both forms (alpha and beta) of the active enzyme are similarly removed from the perfusate. We also observed that the clearance of plasma kallikrein is temperature-dependent, and not affected by substances that inhibit binding to galactosyl-, mannosyl-, fucosyl- or phosphomannosyl-specific lectins, but inhibited by beta-galactosides. We suggest that: (a) the binding site to hepatocytes is latent on prokallikrein and is located on its heavy chain, more specifically on the 28-kDa fragment still present in the beta form of the active enzyme and (b) plasma kallikrein is recognized by an S-type lectin.
Borges
D R
DR
Department of Medicine (Gastroenterology Division), Escola Paulista de Medicina, São Paulo, Brazil.
Kouyoumdjian
M
M
D000577:Amides / Q000378:metabolism; D000818:Animals; D037263:Asialoglycoprotein Receptor; D001665:Binding Sites / Q000502:physiology; D004229:Dithiothreitol; D004591:Electrophoresis, Polyacrylamide Gel; D005174:Factor XII / Q000302:isolation & purification; D006207:Half-Life; D007610:Kallikreins / Q000737:chemistry / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D010446:Peptide Fragments / Q000302:isolation & purification; D010477:Perfusion; D011288:Prekallikrein / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011971:Receptors, Immunologic / Q000378:metabolism*
D000577:Amides; D037263:Asialoglycoprotein Receptor; D010446:Peptide Fragments; D011971:Receptors, Immunologic; D005174:Factor XII; D011288:Prekallikrein; D007610:Kallikreins; D004229:Dithiothreitol