Subject(s)
Endopeptidases/metabolism , Lens, Crystalline/enzymology , Adult , Aged , Animals , Benzoylarginine Nitroanilide/antagonists & inhibitors , Benzoylarginine Nitroanilide/metabolism , Cattle , Enzyme Activation , Humans , Hydrogen-Ion Concentration , Kinetics , Middle Aged , Substrate Specificity , Trypsin/metabolismABSTRACT
The lathyrogens, beta-aminopropionitrile and alpha-aminoacetonitrile inhibit both the esterolytic and proteolytic activity of trypsin at a concentration of 100 mM. Lineweaver-Burk plots demonstrate that inhibition is competitive, with alpha-aminoacetonitrile being the more potent inhibitor. The enzyme associated with and capable of digesting tropoelastin is inhibited by both lathyrogens when tested against its natural substrate, tropoelastin. Administration of alpha-aminoacetonitrile-HCl to the diet of young chicks (0.1% w/w) resulted in a 62% increase in the yield of tropoelastin and significant reduction in fatality as compared to beta-aminopropionitrile-fumarate.
Subject(s)
Acetonitriles/pharmacology , Aminoacetonitrile/pharmacology , Aminopropionitrile/pharmacology , Elastin/analogs & derivatives , Protease Inhibitors , Tropoelastin/metabolism , Trypsin Inhibitors/pharmacology , Trypsin/metabolism , Animals , Benzoylarginine Nitroanilide/antagonists & inhibitors , Binding, Competitive , Chick Embryo , Chickens , Chymotrypsin/antagonists & inhibitors , Fumarates/pharmacology , Pancreatic Elastase/antagonists & inhibitorsABSTRACT
Fitzgerald trait, an asymptomatic disorder, is associated with abnormalities of surface-mediated plasma reactions, including coagulation via the intrinsic pathway, augmentation of the clot-promoting properties of factor VII, kaolin-mediated fibrinolysis, kinin generation, and enhancement of vascular permeability by diluted plasma (PF/Dil). These abnormalities can be corrected by Fitzgerald factor, an agent probably identical with high molecular weight kininogen found in normal, but not Fitzgerald-trait plasma. Our preparations of Fitzgerald factor possessed a second property. Amidolysis of alpha-N-benzoyl-L-proline-L-phenylalanine-L-arginine-pnitroanilide by a plasma kallikrein (activated Fletcher factor) was inhibited by kaolin or solutions of ellagic acid. Addition of preparations of Fitzgerald factor to kaolin or to solutions of ellagic acid counteracted their inhibitory properties. The action of these preparations was duplicated by solutions of cytochrome C or IgG, suggesting that these agents may inhibit the negative charges of kaolin or ellagic acid. Fitzgerald factor enhanced amidolysis of both normal and Fitzgerald-trait plasmas exposed to kaolin, effects not duplicated by cytochrome C or IgG. Whether or not the two properties of our preparations of Fitzgerald factor are related to the same agent is not yet certain. The relationship between these observations and the biologic role of Fitzgerald factor remains to be investigated.
