Plasmin, activity

Generation of plasmin is inhibited by the plasmin-activator inhibitor (PAI). PAI is secreted by endothelial cells. It neutralizes t-PA and u-PA by forming 1 1 complexes. 

Lucas M. A., Fretto L. S., McKee P. A. The relationship of fibrinogen structure to plasminogen activation and plasmin activity during fibrinolysis. Ann N Y Acad Sci 1983 408, 71-91. 

Politis I, Bizelis I, Tsiaras A and Baldi A (2004), Effect of vitamin E supplementation on neutrophil function, milk composition and plasmin activity in dairy cows in a commercial herd , Journal of Dairy Research, 71, 273-278. 

To increase the stability of milk products. Lipoprotein lipase is probably the most important in this regard as its activity leads to hydrolytic rancidity. It is extensively inactivated by HTST pasteurization but heating at 78°C x 10 s is required to prevent lipolysis. Plasmin activity is actually increased by HTST pasteurization due to inactivation of inhibitors of plasmin and/or of plasminogen activators. 

The other major casein in cheese is /3-casein, but it is generally not hydrolyzed by rennet in low-pH cheeses. Alkaline milk protease (plas-min) plays the major role in the hydrolysis of /3-casein (Richardson and Pearce 1981). The plasmin level in cheese is related to the pH of the curd at whey drainage, since plasmin dissociates from casein micelles as the pH is decreased. Richardson and Pearce (1981) found two or three times more plasmin activity in Swiss cheese than in Cheddar cheese. Swiss cheese curds are drained at pH 6.4 or higher, while Cheddar cheese curds are drained at pH 6.3 or lower. Proteolysis of /3-casein is significantly inhibited by 5% sodium chloride. The inhibitory influence of sodium chloride is most likely due to alteration of /3-casein or a reduction in the attractive forces between enzyme and substrate (Fox and Walley 1971). 

The gross proteolysis of casein is probably due solely to rennet and plasmin activity (O Keeffe et al. 1978). Bacterial proteases and peptides are responsible for subsequent breakdown of the large peptides produced by rennet and plasmin into successively smaller peptides and finally amino acids (O Keeffe et al. 1978). If the relative rate of proteinase activity by rennet, plasmin, and bacterial proteases exceeds that of the bacterial peptidase system, bitterness in the cheese could result. Bitter peptides can be produced from a,-,- or /3-casein by the action of rennet or the activity of bacterial proteinase on /3-casein (Visser et al. 1983). The proteolytic breakdown of /3-casein and the subsequent development of bitterness are strongly retarded by the presence of salt (Fox and Walley 1971 Stadhouders et al. 1983). The principal source of bitter peptides in Gouda cheese is 3-casein, and more particularly the C-terminal region, i.e., 3(193-209) and 3(193-207) (Visser et al. 1983). In model systems, bitter peptides are completely debittered by a peptidases system of S. cremoris (Visser et al. 1983). 

Stanazol [10418-03-8] -plasmin activation [BLOOD, COAGULANTS AND ANTICOAGULANTS] (Vol 4)... 

Lei, H., Romeo, G. and A. Kazlauskas, 2004, Heat shock protein 90alpha-dependent translocation of annexin II to the surface of endothelial cells modulates plasmin activity in the diabetic rat aorta. Circ. Res. 94, 902-909. 

Bugaud, C., Buchin, S., Coulon, J.B., Hauwuy, A., Dupont, D. 2001. Influence of the nature of alpine pastures on plasmin activity, fatty acid and volatile compound composition of milk. Le Lait. 81, 401 414. 

Alpha 2-antiplasmin and alpha 2-macroglobulin. These inactivate plasmin. Plasmin activity is also reduced by thrombin-activatable fibrinolysis inhibitor, which modifies fibrin to make a less potent co-factor for the t-PA-mediated plasminogen. 

The minor coagulation processes constantly taking place in the vascular system (whereby fibrin is deposited) are counteracted by simultaneous fibrinolysis. Coagulation and fibrinolysis are thus in continuous dynamic balance. Plasminogen is converted to plasmin by activators such as urokinase PA (isolated from urine) and tissue PA (isolated from tissue). The effect of tissue PA is strongly enhanced by the presence of fibrin. Fibrinolysis is stimulated by protein C, while plasmin activity is maintained in balance by inhibitors (e.g. a2-antiplasmin, a2-macroglo-bulin). (s.fig. 19.1)... 

Chakravarty RK, Carl PL, Weber MJ, et al. Plasmin activated prodrugs for cancer chemotherapy. 1. Synthesis and biological activity of peptidylacivicin and peptidylphenyle-nediamine mustard. J Med Chem 1983 26 638-644. 

From the above, one can appreciate the complexities in designing a synthetic substrate assay for plasminogen and plasmin. Friberger has recommended certain guidelines in his recent review (F5). Most workers prefer SK over the other available activators. Latallo reported a total evaluation of the fibrinolytic system in patients (L7). This profile included the measurement of free plasmin activity and the concentration of plasminogen, its activators and inhibitors. A fully automated assay for plasminogens on a clinical analyzer has also been reported (PI). Comparison of the synthetic substrate... 

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