Serine proteases, plasma

Indeed, the structural requirement for the interaction of these SPs with the coagulation cofactors and their target proteases and inhibitors are stereospecific (Mourao, 2004 Mourao and Pereira, 1999 Pomin, 2008 Pomin and Mourao, 2008). The site of sulfation has a major impact on activity. This can be illustrated by the fact that 2,4-di-sulfated units have an amplifying effect on the AT-mediated anticoagulant activity in the series of 3-linked a-L-fucans (Fig. 12.1 Table 12.1). Specific sulfation sites are required for the interaction with plasma serine-protease inhibitors. Note the occurrence of the 4-sulfated unit content in the... 

Fig. 1. Summary of the action of serine proteases on normal and abnormal cells, for example cancer cells. Pathogens activate inflammatory cells and foreign serine proteases mediate the invasion of healthy cells. Activated inflammatory cells release a serine protease to destroy pathogens and activate the inflammatory response of normal cells. The inflammatory response is shut down by Bik after release from the inter-a-inhibitor. Above dashed line Bik is linked to HI and H2 heavy chains or just an H3 chain the two forms are found primarily in plasma. Serine protease splits Bik as shown in the figure to form Bik with N- or O-linked glycosides that are primarily found in urine. As Bik fragments further into Uri (various Bik without O-linked glycosides), the amount in urine increases over the amount found in blood.

Antithrombin-III (11) and only a portion of this, probably only one or two chains, converts Antithrombin-III into an immediate inhibitor of the enzyme thrombin (14). The chains optimal for this do not appear to be identical to those optimal for USP anticoagulant activity or to those optimal for production of inhibitor activity against other important plasma serine proteases (coagulation Factor Xa, etc.). 

The quantification of kinins in human tissues or body fluids has been limited due to the inherent difficulties in accurately measuring the concentration of ephemeral peptides. Today HPLC-based and RIA/capture-ELA measurements are established to determine kinins in human plasma, liquor or mine. Serine protease inhibitors need to be added to prevent rapid degradation of the kinins in vitro during sample preparation. Kinins and their degradation products have been studied in various biological milieus such as plasma/ serum, urine, joint fluids, kidney, lung and skeletal muscle [2]. Under normal conditions, the concentration of kinins in these compartments is extremely low for... 

OCi-Antitrypsin is the major serine protease inhibitor of plasma, in particular inhibiting the elastase of neu-... 

Cl-Inh belongs to a superfamily of serine protease inhibitors (serpins) and is a major inhibitor of F-XIIa and kallikrein. It is also an inhibitor of activated complement factors C1 q, C1 r, and C1 s. C1 -Inh thus regulates the activation of two important plasma cascade systems. Proteases induce a conformational change in the plasma protein a2-M, which results in entrapment of the protease into the a2-M cage (B4). In vivo, a2-M acts as a second inhibitor of kallikrein. 

Urokinase is a serine protease produced by the kidney and is found in both the plasma and urine. It is capable of proteolytically converting plasminogen into plasmin. Two variants of the enzyme have been isolated a 54 kDa species and a lower molecular mass (33 kDa) variant. The lower molecular mass form appears to be derived from the higher molecular mass moiety by proteolytic processing. Both forms exhibit enzymatic activity against plasminogen. 

Vertebrates contain several proteins that maintain the integrity of the blood plasma circulatory system. These contain domains that are specific to vertebrates (Gla, FN1, FN2) (Patthy, 1985), domains that are found in different contexts in invertebrates and/or protists (FBG, APPLE, KR) (Xu and Doolittle, 1990 Eschenbacher et al., 1993 Wilson et al., 1993) and a domain that is found in all cellular life (trypsin-like serine protease, Tryp SPc). The invertebrate versions of these domains, however, are found in molecular contexts that differ considerably from their vertebrate extracellular counterparts, indicating that although these nonenzy-... 

Circulahng plasmin is rapidly neutralized by aj-an-tiplasmin, a physiological serine protease inhibitor that forms an inert complex with plasmin. In contrast, hbrin-bound plasmin is resistant to inactivation by 2-an-tiplasmin. Under normal circumstances plasma t-PA is inactive because it is inhibited by PAI-1, while t-PA that is bound to hbrin is unaffected by PAI-1. In addition, plasma t-PA has a very rapid turnover in blood (half-life 5 to 8 minutes). For these reasons, hbrinolysis is normally restricted to the thrombus. 

Urokinase (Abbokinase) is a two-polypeptide chain serine protease that does not bind avidly to hbrin and that directly activates both circulating and hbrin-bound plasminogen. The plasma half-life of urokinase is approximately 10 to 20 minutes. Urokinase is derived from human cells and thus is not anhgenic. Urokinase produces a signihcant resolution of recent pulmonary emboli. 

Inieraciions of the serine proteases with active-si ic di reeled inhibiiois me blocked by acylation. Therefore, in contrast to the active enzyme, the acyl enzyme is protected from being inactivated in plasma by rapidly acting inhibitors (protection against inactivation). 

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