The main function of plasmin

The human body contains many trace elements and many enzymes that promote chemical reactions in the body. The enzymes in the human body can only exert their best activity and promote chemical reactions in the human body at a temperature of 37 degrees Celsius. Plasmin is also an enzyme in the human body. The main component of enzymes is protein. Next, I will introduce to you the main function of plasmin.

Plasmin is a proteolytic enzyme that can specifically degrade fibrin gel and is an important component of the fibrinolytic system. The coagulation and fibrinolysis systems in the body are interdependent and closely linked. Once the body produces a coagulation reaction, the fibrinolytic system is almost simultaneously activated to remove excess blood clots in the body and reduce the level of fibrinogen in the body through a negative feedback effect, thereby avoiding excessive coagulation of fibrin.

What it does

1. Degradation of fibrin and fibrinogen

2. Hydrolyze multiple coagulation factors (Ⅱ.Ⅴ.Ⅶ.Ⅷ.Ⅹ.Ⅺ)

3. Convert plasminogen into plasmin

4. Hydrolysis of complement, etc.

Fibrinolytic process

The entire fibrinolytic process includes two parts, namely the activation of plasminogen and the degradation of fibrin or fibrinogen.

activation

Plasminogen has two activation pathways: endogenous and exogenous. ① Endogenous activation: refers to the presence of activating factors in the blood that can activate plasminogen. It may come from the endothelial cells of veins or venules. Its activity in the veins of the upper limbs is higher than that in the veins of the lower limbs. This is one of the reasons why venous thrombosis in the lower limbs is more common than that in the veins of the upper limbs. In addition, there is an activated factor progen in the blood. Once the body's coagulation reaction is initiated, one of the activated coagulation factors, coagulation factor XI, not only participates in its own coagulation system, but also activates this activated factor progen, which further activates plasminogen. The activated factor pro in the blood is easily adsorbed by the fibrin clot, thus facilitating the dissolution of the thrombus. ② Exogenous activation: It is achieved through tissue activation factor, which is particularly abundant in uterine, ovarian, kidney and lung tissues. Differentiated cells in the early stages of malignant tumors and differentiated cells during fetal development can also release a large number of activation factors. In addition, activating factors are also present in secretions such as urine, saliva, milk, bile and prostate. In particular, the activating factor in urine is called urokinase, with a molecular weight of 54,000. This enzyme has been highly purified and is the most studied of the plasminogen activating factors. Some bacteria can also produce activating factors, such as streptokinase secreted by streptococci. Urokinase and streptokinase are both effective antithrombotic drugs.

The primary structure of plasminogen has been fully elucidated. It is a peptide chain containing 790 amino acid residues with glutamic acid at the N-terminus. Urokinase can activate plasminogen in two different ways (Figure 1): ① Urokinase specifically cleaves the peptide bond between residues Arg-Val (560-561), activating it into plasmin with glutamic acid at the N-terminus. The latter then cleaves itself and acts on the peptide bond Lys-Lys (77-78) or Lys-Val (78-79) near the N-terminus, releasing the corresponding peptide fragments, and finally forming plasmin with Lys or Val at the N-terminus. This activation pathway is relatively slow; ② The small amount of plasmin formed in the body first degrades the zymogen, removing the peptide fragment of 77 or 78 amino acid residues from the N-terminus, forming plasminogen with Lys or Val at the N-terminus. At this time, due to the change in conformation, it is easier to be activated by urokinase than the intact plasminogen, and finally forming plasmin with Lys or Val at the N-terminus.

The activation of plasminogen by streptokinase is a contact activation. Streptokinase itself is not an enzyme, but a protein with a molecular weight of 47,000. It combines with plasminogen to form an equimolar complex, which changes the conformation of plasminogen in the complex and exhibits the activity of an activation factor. It catalyzes the remaining free plasminogen and converts it into plasmin.

After activation, plasmin forms two peptide chains linked by two pairs of disulfide bonds. The light chain is the C-terminal part of the original peptide chain, containing a total of 230 amino acid residues. Its structure is similar to that of trypsin, and the active site of the enzyme is located in the light chain. The N-terminus of the heavy chain is lysine or valine, and the C-terminus is arginine, which is the site of peptide bond cleavage during activation. The structure of this heavy chain portion is very similar to the A and S-peptide segments at the N-terminus of prothrombin and is composed of five similar ring structures, also known as the "ring cake" structure (Figure 2). The five ring structures are likely connected and may be produced by repeated expression of the same gene. It is still unclear what functional significance the special characteristics of the ring-shaped cake structure have. Some people believe that the adsorption of plasmin by fibrin gel in vivo is likely related to this structure.

Human plasma α2-globulin contains an inhibitor that specifically inhibits plasmin, called α2-plasmin inhibitor (α2-PI). It has a strong affinity for plasmin and can instantly form a complex to inactivate the enzyme. In addition, α2-macroglobulin and α1-antitrypsin in plasma can also inhibit plasmin to a certain extent, but they only work when there is excess plasmin and insufficient α2-PI.

degradation

As plasmin gradually degrades fibrin, it releases five corresponding degradation fragments A, B, C, D, and E. A, B, and C are small molecules, and D and E are large molecules. The molecular weights of fragments D and E are 80,000 and 48,000, respectively. The molecular weight of fragment D is about twice that of fragment E. In addition, intermediate fragments "X" and "Y" with larger molecular weights can be obtained. It can be inferred that the degradation process of fibrin is as follows: fibrin degrades into "X" fragments and releases small molecule fragments "A" and "B", which are equivalent to about 40 to 50 amino acid residues at the N-terminal part of the fibrin β peptide chain and the loose part at the C-terminal end of the α peptide chain, respectively. The "X" fragment is further degraded into "D" and "Y" fragments. The D fragment is equivalent to the C-terminal main body of the fibrin monomer, while the E fragment is equivalent to the middle main part of the fibrin monomer, including the structure of the disulfide bond section. The "C" fragment is the middle helical region structure connecting the N-terminal and C-terminal main parts of fibrin.

Although the fragments of the above degradation products are not homogeneous, they can be clearly distinguished from each other in electrophoresis, ultracentrifugation sedimentation and immunological characteristics. Among them, the large molecular weight degradation products, especially fragment "Y", have obvious anticoagulant effect, which can competitively inhibit thrombin activity and prevent the polymerization of fibrin monomers, thereby preventing further formation of fibrin gel in the body. This is actually a negative feedback effect of self-regulation.