Blood-clotting enzymes

Mann KG, Jerry RJ, Krishnaswamy S. Cofactor proteins in the assembly of blood clotting enzyme complexes. Annu Rev Biochem 1988 57 915-956. 

Usually catalysts and enzymes are very specific and will only speed up one particular reaction. For example, one enzyme in the blood will only catalyse one type of reaction and will not affect other reactions. Therefore a blood clotting enzyme reacting at the site of a cut will not be affected by a clot dissolving enzyme at a different site. The reactions are very specific. 

A. Blood Clotting Enzyme Factor Xa, FXa, or Factor VIIa, FVIIa Inhibitors... 

V-Guanidinoal kvI amides analogs of the current invention, (n), prepared by Klingler (2) were effective as reversible inhibitors of the blood clotting enzymes factor Xa and/or factor Vila and used in the treatment of thromboembolic diseases or restenosis. 

Enzymes. Normal plasma contains only a few esterases in addition to ceruloplasmin and the blood clotting enzymes. However, in certain pathologic conditions enzymes from tissue can enter the blood plasma examples are glutamate-oxaloace-tate transaminase (with cardiac infarction) or lactate dehydrogenase (with several liver diseases). Hence, enzyme assays in plasma have acquired diagnostic value. 

Calcium is essential to several steps in the enzyme cascade of the blood clotting process, such as the conversion of prothrombin to thrombin (23). Clotting can be inhibited in stored blood suppHes by addition of complexing agents such as EDTA or citrate which reduce the levels of the free ion, Ca(Il). 

FIGURE 18.40 The glutamyl carboxylase reaction is vitamin K-dependent. This enzyme activity is essential for the formation of 7-car-boxyglutamyl residues in several proteins of the blood-clotting cascade (Figure 15.5), accounting for the vitamin K dependence of coagulation. 

Although the exact action of the thrombolytic dragp is slightly different, these drugs break down fibrin clots by converting plasminogen to plasmin (fibrinolysin). Plasmin is an enzyme that breaks down the fibrin of a blood clot. This reopens blood vessels after their occlusion and prevents tissue necrosis. 

The serine proteases are the most extensively studied class of enzymes. These enzymes are characterized by the presence of a unique serine amino acid. Two major evolutionary families are presented in this class. The bacterial protease subtilisin and the trypsin family, which includes the enzymes trypsin, chymotrypsin, elastase as well as thrombin, plasmin, and others involved in a diverse range of cellular functions including digestion, blood clotting, hormone production, and complement activation. The trypsin family catalyzes the reaction ... 

Recently, a superior therapy has been approved for use by the federal government tissue-type plasminogen activator (tPA). This naturally occurring enzyme dissolves blood clots as part of the normal healing process. By administering relatively large quantities of it, clot breakdown time can be shortened from about a week to under an hour. 

Biomaterials cover a broad range of properties from those that are designed to be inert to those that are intended to elicit a particular set of biological responses. In the latter category are materials with surfaces tailored to retard blood clotting, or surfaces that bear covalently bound bioactive agents such as enzymes or antigens. 

Certain enzymes, proenzymes, and their substrates are present at all times in the circulation of normal individuals and perform a physiologic function in the blood. Examples of these functional plasma enzymes include lipoprotein Upase, pseudocholinesterase, and the proenzymes of blood coagulation and blood clot dissolution (Chapters 9 and 51). The majority of these enzymes are synthesized in and secreted by the liver. 

Ionized calcium is an important regulator of a variety of cellular processes, including muscle contraction, stimulus-secretion coupling, the blood clotting cascade, enzyme activity, and membrane excitability. It is also an intracellular messenger of hormone action. 

K Phylloquinone, menaquinones Coenzyme in formation of y-carboxyglutamate in enzymes of blood clotting and bone matrix Impaired blood clotting, hemorrhagic disease... 

A number of iron-containing, ascorbate-requiring hydroxylases share a common reaction mechanism in which hydroxylation of the substrate is linked to decarboxylation of a-ketoglutarate (Figure 28-11). Many of these enzymes are involved in the modification of precursor proteins. Proline and lysine hydroxylases are required for the postsynthetic modification of procollagen to collagen, and prohne hydroxylase is also required in formation of osteocalcin and the Clq component of complement. Aspartate P-hydroxylase is required for the postsynthetic modification of the precursor of protein C, the vitamin K-dependent protease which hydrolyzes activated factor V in the blood clotting cascade. TrimethyUysine and y-butyrobetaine hydroxylases are required for the synthesis of carnitine. 

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