Metabolism of Macromolecular Heparin in Murine Neoplastic Mast Cells

Abstract

Most glycosaminoglycans occur in the native state as proteoglycans, composed of several polysaccharide chains covalently linked to a common polypeptide core (9). Attempts to isolate a heparin proteoglycan have been unsuccessful,yielding essentially single polysaccharide chains, with molecular weights ranging from 7,000 to about 25,000 (6,10). However, in rodent tissues heparin has been shown to occur as a multichain, macromolecular species (molecular weight up to 10⁶) distinctly different from a conventional proteoglycan (4, 10); in this molecule, the individual polysaccharide chains are joined in an unknown manner, possibly by a polysaccharide core (4). The results of Horner suggest that the macromolecular heparin represents a precursor form of the polysaccharide, which must be depolymerized to acquire biological activity (5). The present investigation was undertaken in order to obtain experimental evidence for the postulated conversion in vivo of the macromolecular precursor (in the following denoted “macromolecular heparin”) to the low-molecular heparin product (“conventional heparin”). In addition, the enzyme responsible for this degradation was isolated and characterized in some detail.