Heparin specificity

Toma L, Berninsone P, Hirschberg CB. The putative heparin-specific A-acetylglucosaminyl A-deacetylase/N-sulfotransferase also occurs in non-heparin-producing cells. J. Biol. Chem. 1998 273(35) 22458-22465. 

Patients with end-stage renal failure may require monitoring with an anti-factor Xa assay because this condition may prolong the half-life of low-molecnlar-weight heparin. Specific dosage recommendations for varions low-molecnlar-weight heparins may be obtained from the mannfactnrer s literature. 

Barzu T, Van Rijn JL, Petitou M, MoUio P, Tohelem G, Caen JP. Endothelial binding sites for heparin. Specificity and role in heparin neutrahzation. Biochem J 1986 238 847-54. 

Affinity chromatography is used in the preparation of more highly purified Factor IX concentrates (53—55) as well as in the preparation of products such as antithrombin III [9000-94-6] (56,57). Heparin [9005-49-6], a sulfated polysaccharide (58), is the ligand used most commonly in these appHcations because it possesses specific binding sites for a number of plasma proteins (59,60). 

Prourokinase is a single-chain protein containing 411 amino acids (261,265,274,275). In clinical uses scu-PA does not bind to fibrin only and its use causes a decreased plasma fibrinogen of 80%. Its half-life in the circulation is 5 min. It is cleared by the fiver. It is used at 40—70 mg over 1 h and heparin is needed simultaneously. Fibrin specificity and thrombolytic efficacy are similar to that of t-PA. 

Heparin is an important anticoagulant. It binds with factors IX and XI, but its most important interaction is with plasma antithrombin III (discussed in Chapter 51). Heparin can also bind specifically to lipoprotein lipase present in capillary walls, causing a release of this enzyme into the circulation. 

The endogenous activity of antithrombin III is gready potentiated by the presence of acidic proteoglycans such as heparin (Chapter 48). These bind to a specific cationic site of antithrombin III, inducing a conformational change and promoting its binding to... 

The multiple effects of UFH on the coagulation cascade may increase its potential to cause hemorrhage." Anticoagulants with more specific sites of action may confer a better safety profile. Two such anticoagulants are low-molecular-weight heparin (LMWH) and heparinoids. 

Heparinoid is a term used to describe naturally occurring and synthetic glycosoaminoglycans of structure similar to heparin. Heparinoids have specific... 

It is important to note that the foregoing, biosynthetic-polymer modification is usually incomplete. In fact, only a fraction of the heparin precursor undergoes all of the transformations shown in Scheme 1. However, as the product of each enzymic reaction constitutes the specific substrate for the succeeding enzyme, the biosynthesis of heparin is not a random process. Thus, sulfation occurs preferentially in those regions of the chain where the amino sugar residues have been N-deacetylated and N-sulfated, and where D-glucuronic has been epimerized to L-iduronic acid.20... 

Heparin is most commonly prepared as the sodium salt, which can be converted into other salts (usually potassium or calcium) by cation exchange.45 For the sake of simplicity, the term heparin will be used throughout this article, instead of the more appropriate term sodium heparinate. Mention of a specific cation other than sodium will be made only when relevant to the property discussed. 

For detailed description and discussion of methods of separation and characterization of GAG, the reader is referred to specific mono-graphs38-42-46-47 dealing with the advantages and drawbacks of different colorimetric, titrimetric, electrophoretic, chromatographic, spectroscopic, and enzymic methods for the qualitative and quantitative characterization of heparin and its most common contaminants. The present article is concerned only with analytical aspects of relevance to the structural characterization of heparin. 

Although widely used, colorimetric methods for determining total ur-onic acid and hexosamine are now regarded as providing, at best, only semi-quantitative estimates of heparin.42 Colorimetric reactions in a strong acid, such as the carbazole reaction for the uronic acids48 and the Morgan-Elson reaction for the hexosamines,49 are not specific for hepa-... 

More-specific methods are available for identifying and quantitating the typical, amino sugar component of heparin (and some heparan sulfate species), namely, 2-deoxy-2-sulfoamino-D-glucose. Most of these methods are based on conversion of these residues into 2,5-anhydro-D-mannose by deamination with nitrous acid (see Section VIII,2). The 2,5-anhydro-D-mannose residues may be determined either colorimetrically,52-54 or fluorimetrically.55... 

Nuclear magnetic resonance (n.m.r.) spectroscopy provides the most-specific and informative spectra of heparin and related... 

A classical, and still most useful, physicochemical parameter for characterizing glycosaminoglycans is their specific optical rotation. For pure heparins from common sources, [a]80 = + 45 to + 53 ° (see Table II). The actual value depends on the relative proportions of monosaccharide constituents (that is, the L-idosyluronic acid residues make a less positive contribution than the n-glucosyluronic residues), and on the degree of sulfation of the preparation (that is, although sulfate groups may have little direct influence on the molecular rotation, they lower the value by acting as diluents ). 

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