Heparin lyase I (EC 4.2.2.7), initially labeled heparinase, has been immunopurified and acts on 1→4 glucosaminido-iduronic acid linkages. The main degradation products formed by the action of this enzyme are trisulfated disaccharide and sulfated tetrasaccharides. Unlike heparin lyase I, heparin lyase II is able to cleave tetrasaccharides produced from heparin lyase I digests of heparin. The sulfated tetrasaccharides are degraded forming tri- and disulfated disaccharides. Heparin lyase II, besides having heparinase I substrate specificity also degrades all but two α- glucosaminido bonds in heparin and heparan sulfate. The two resistant bonds involve the glucuronic acid adjacent to the GlcNS3S residue in the antithrombin III(AT)-binding region, and the glucuronic acid in the linkage region. Heparin lyase III prefers to degrade GlcNAc→GlcA or GlcNAc6S→GlcA bonds and the above linkage region but not the Glc2S residue adjacent to the GlcNS3S residue in the AT-binding region.

The spectrum of saccharide sequences extends from the nonsulfated →GlcA→GlcNAc→ disaccharide unit, which is commonly found in heparan sulfate, to the highly sulfated →IdoA2S→GlcNS6S→ sequence which is the predominant component of heparin. Heparan sulfate sequences with a high content of the unusual →Glc2S→GlcNS6S→ disaccharide unit accumulates in the nuclei of hepatocytes and are proposed to be involved in the growth control of the cells. No ligand interacting with this structure has yet been identified.

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