title: Arginine inhibits serpins.
abstract: Serine protease inactivators (serpins) are important regulators in biochemistry. Often it is necessary to block the serpin action, that is, to stabilize the sample. The guanidine group of arginine is the ligand for the active center pocket of many serine proteases. Arginine or guanidine inhibits serine proteases, and arginine belongs to the reactive P1-P1' center of many serpins. The plasmatic antithrombin, antiplasmin, or anti-C1-esterase activity was determined: A total of 20 microL of pooled normal plasma or 7% human albumin was added to 100 microL of 0-2.67 M arginine, pH 8.6, 10 microL of 26 mIU/mL thrombin in 7% human albumin, and 30 microL of 1.7 mM CHG-Ala-Arg-pNA (37 degrees C). DeltaA at 405 nm was determined, by using a microtiter plate reader. Thrombin was substituted by plasmin or C1-esterase, and the chromogenic peptide substrates <Glu-Phe-Lys-pNA or MeOC-Lys(eCBO)-Gly-Arg-pNA, respectively, were used. The IC(50) of arginine against plasmatic antithrombin activity is 580 mM; the IC( 25) is 440 mM. The IC(25) of arginine against plasmatic alpha( 2)-antiplasmin or C1-inactivator is 1650 mM. The amidolytic activity of thrombin, plasmin, and C1-esterase is inhibited similarly by arginine: the IC(50) for arginine against the amidolytic activity of these proteases is about 400 mM. Arginine at very high concentrations inhibits serpins. This is important, if stabilization of a biological fluid is a prerequisite for valid activities of serine proteases. In addition, these high concentrations of arginine might be a new gentle principle to inhibit pathogens that need serpins for their pathophysiology.
authors: Department of Clinical Chemistry, University Hospital, Giessen/Marburg, Germany, thstief@med.uni-marburg.de
authors: Thomas W
authors: TW
authors: Stief
mesh_terms: D001120:Arginine / Q000494:pharmacology*; D006801:Humans; D015843:Serpins / Q000378:metabolism*; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000378:metabolism; D000979:alpha-2-Antiplasmin / Q000378:metabolism
chemical_list: D015843:Serpins; D000979:alpha-2-Antiplasmin; D001120:Arginine; D013917:Thrombin