Plasmin is a protein-cleaving enzyme of human blood serum that is formed from the precursor plasminogen. Its main function is fibrinolysis and thus the endogenous breakdown of blood clots. Overactivity of plasmin can lead to bleeding tendency and underactivity to thrombus tendency.
What is plasmin?
Human blood serum contains various proteins and enzymes. Enzymes consist of giant biological molecules and act as catalysts to accelerate chemical reactions. Nearly all enzymes in human blood are proteins formed by protein biosynthesis of ribosomes. Enzymes have a wide variety of tasks in the organism. Depending on their function, they are further classified. Peptidases, for example, are a group of enzymes that cleave peptides or proteins. In this way, they catalyze the hydrolysis of peptide compounds. Peptidases are also called proteolytic enzymes. One such proteolytic enzyme is plasmin. It is found in blood serum and cleaves various proteins there. It is also responsible for breaking down proteins from the serum. Plasmin is formed from the precursor plasminogen.
Function, action, and tasks
The main function of plasmin is fibrin cleavage. This process, known as fibrinolysis, plays a role primarily in blood clots. In this process, plasmin dissolves endogenous blood clots by breaking down the fibrin polymers of the thrombus into fibrin degradation products. Fibrinolysis is regulation by opposing biochemical processes. Activation occurs through the conversion of inactive plasminogen to active plasmin. Fibrinolysis becomes active along with blood clotting, but progresses significantly more slowly. Two endogenous activators are involved in the activation of fibrinolysis: tissue-specific plasminogen activator and urokinase. Non-physiological activators involved in plasmin activation are staphylokinase and streptokinase. The exogenous activators form a larger complex with plasminogen and plasmin that activates inactive plasminogen. PAI-1 to PAI-4 appear as inhibitors of fibrinolysis activation. Plasmin cleaves fibrin polymers after activation. It binds to fibrin and separates the branched fibrin polymers into soluble degradation products with different structure and mass. Blood circulation removes the soluble materials until they are flushed from the bloodstream. To deactivate fibrinolysis, the body resorts to the plasmin inhibitor alpha-2 plasmin inhibitor. Fibrin-bound plasmin has a relatively long half-life compared to this antiplasmin. However, free plasmin is rendered harmless in the serum by the inhibitor within a very short time. Plasmin thus takes on important tasks in the coagulation system and acts as an antagonist of thrombin. In addition to fibrin, the precursor fibrinogen is also broken down by plasmin and its precursor. Serine proteases such as plasmin have an irreversible effect and do not catalyze biochemical reactions in both directions. Plasmin has autocatalytic activity and converts other molecules into active plasmin. Accordingly, its proenzyme is a substrate of the activated one. Apart from its fibrinolytic activity, plasmin also cleaves proteins such as activated collagenases. In addition, it activates various mediators in the complement system and thins the wall of Graafian follicles during ovulation.
Formation, occurrence, properties, and optimal levels
Plasmin is formed from the precursor plasminogen. It is synthesized in the liver and subsequently released into the bloodstream, where it is measurable. Plasminogen has a half-life of more than two days. Free plasmin is hardly, if at all, detectable in the blood. Only plasminogen can be determined. The determination usually takes place in citrated blood. The standard values for plasminogen activity are between 85 and 110 percent. For plasminogen concentration, the standard value is 0.2 g per liter. Plasminogen becomes plasmin, which, like elastase and trypsin, corresponds to an endopeptidase. Activation of plasminogen to plasmin occurs by various substances. The most important are tPA, thrombin, factor XII and fibrin. As part of the peptidase subgroup serine protease, plasmin has an active site. In this active site, serine proteases carry a catalytic triad involving the amino acid serine.The catalytic triad of aspartic acid, histidine, and serine contains amino acid residues cross-linked by hydrogen bonds.
Diseases and disorders
One plasmin-related disorder is plasminogen activator inhibitor-1 deficiency. This congenital deficiency leads to premature dissolution of blood clots, resulting in a bleeding tendency. PAI-1 appears in the healthy body as an inhibitor of tissue-type plasminogen activator, as it plays a role in intravascular fibrinolysis. Spontaneous bleeding is rarely a symptom of the disease. Nonetheless, minor trauma can cause bleeding from the knees, elbows, nose, or gums. Menstrual bleeding is often increased. Long periods of bleeding after surgery are often observed in patients. If there is only a partial inhibitor deficiency, bleeding is less frequent. Bleeding may not occur at all or may be light. In some patients, the inhibitory protein is present but does not function. The cause is a mutation of the associated alleles. The disease of the homozygous state is based on an autosomal recessive inheritance. ELISA antibody test or analysis of PAI-1 function allows diagnosis. As a countermeasure to the bleeding tendency, patients are administered fibrinolysis inhibitors such as epsilon-amino caproic acid or tranexamic acid. A mutationally reduced activity of plasmin is the opposite of the disease described and may promote a thrombotic tendency. Modern medicine also assumes that the degradation of connective tissue by the enzyme plasmin plays an important role in the spread of various diseases. Associated diseases now include cancer, cardiovascular disease, and inflammation.