Plasminogen and Plasmin as Key-Substances within the Fibrinolytic System

Abstract

Plasminogen and plasmin are important proteins of the fibrinolytic system since they constitute a proteolytic mechanism which is responsible for the digestion of fibrin. The central event is the activation of plasminogen to the active protease plasmin by the action of activators which are widely distributed in the organism. Fibrinolysis is regulated by inhibitors influencing either the activation step or the generated plasmin activity. 
Plasminogen is isolated by affinity chromatography using as the functional group of the adsorbent 6-aminohexanoic acid which is known to form complexes with plasminogen and plasmin. Plasminogen (mol. weight ~92000) consists of a single polypeptide chain with NH₂-terminal Glu and COOH-terminal Asn. During the two-step activation, peptide material is liberated from the NH₂-terminal end of the original polypeptide chain and the cleavage of an Arg-Val bond in its COOH-terminal half produces the active, two-chain plasmin. The heavy chain (mol. weight ~59000) has NH₂-terminal Lys and COOH-terminal Arg and the light chain (mol. weight ~25000) which is the carrier of the active center, has NH₂-terminal Val and COOH-terminal Asn. The two chains are covalently linked apparently by two disulfide bridges. Two mechanisms of activation are discussed which differ in the nature of an intermediate product and in the sequence of events, but finally lead to the same end product. The primary structure of plasminogen and plasmin is known to a large extent. The catalytically functional part, the light chain, shows similarities to trypsin and other pancreatic proteases which are particularly evident from sequence homology in the vicinity of the essential Ser and His residues of the active center. The heavy chain contains up to five regions with an internal sequence homology which are in addition homologous to two regions in the “pro-part” of prothrombin.