Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5667_Библиотеки_им_академика_М_И_Перельмана

Following mast cell activation and consequent degranulation, heparin is released in the extracellular matrix of endothelium and partially hydrolyzed by heparanase, an endo-β-glucuronidase into fragments ranging in mass from 5 to 30 kDa[10], resulting in a mixture of highly heterogenous polymeric chains arising from both the different molecular weight as well as the number and position of sulfate groups of the constituent disaccharides. The main repeating disaccharide structure of the resulting polymer is the trisulfated unit [-4)-α--IdoA2S (1→4) α--GlcNS,6S-(1-], which constitutes the regular polymer regions, accounting for more than 70% of heparin chains and resulting in an overall degree of sulfation of about 2.4 per disac­charide[11, 12]. The remaining 30% of the heparin polymer, constituting the so­called irregular regions, has a more complex composition, including both less O-sulfated and N-acetylated domains, and an important pentasaccharide sequence, containing a 3-O-sulfated glucosamine, which interestingly, is usually preceded by an un-sulfated IdoA residue, IdoA–[GlcNAc,6S–GlcA–GlcNS,3S,6S–IdoA2S– GlcNS,6S–][13, 14]. Such a pentasaccharide, also called AGA*IA, with the asterisk indicating the peculiar 3-O sulfation, is endowed with a high affinity for the plasma protein AT. The structures of the basic disaccharide units, together with the AT-binding pentasaccharide are shown in Figure11.1. Despite the observation that irregular regions do not appear to be distributed in an orderly manner, a low- sulfated domain resides close to the original heparin core protein [15]. Moreover, the 3-O-sulfated pentasaccharide turns out to be enriched toward the nonreducing ter­minus of the heparin chain[16–19], in agreement with the finding that NMR sig­nals typically associated with the “linkage region” [20] are missing in heparin fractions with high affinity for AT[21]. In contrast, other studies have suggested a random distribution[22].