A proteoglycan form of heparin and its degradation to single-chain molecules.
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Macromolecular heparin, isolated from rat skin, was found by ultracentrifugation to have a molecular weight of >900,000. After treatment of this material with nitrous acid, a core fraction (M(r)~20,000) was isolated that contained more than 90% of the neutral sugars (xylose and galactose) and amino acids (essentially serine and glycine) of the total reaction products but less than 4% of the uronic acids. Analytical data for the core fraction indicated about 15 carbohydrate-peptide linkage regions/molecule and, in addition, 1 or 2 uronosyl-N-acetylglucosamine disaccharide units for each linkage region. Treatment of the rat skin heparin with alkali in the presence of sodium [3H]borohydride resulted in degradation of the material to single polysaccharide chains along with destruction of about 70% of the serine residues; the glycine residues remained intact but largely lost their covalent association to the polysaccharide. Molecular weights for the liberated chains, calculated on the basis of ultracentrifugation analysis, the amount of serine destroyed, or the amount of [3H]xylitol formed, ranged between 60,000 and 100,000. Incubation of such chains with a mastocytoma endoglycosidase previously implicated in the postbiosynthetic modification of heparin yielded partially depolymerized products with a molecular weight approaching that of commercially available heparin (7,000 to 25,000). It is proposed that rat skin heparin occurs as a proteoglycan with a polypeptide core composed of alternating serine and glycine residues, in which at least 2 out of 3 serine residues are substituted with polysaccharide chains. Furthermore, it is suggested that this proteoglycan may represent a common product of heparin biosynthesis and that the small molecular, single-chain heparin that occurs in various tissues is formed by limited cleavage of proteoglycans by endoglycosidases.
author list (cited authors)
Robinson, H. C., Horner, A. A., Höök, M., Ogren, S., & Lindahl, U
complete list of authors
Robinson, HC||Horner, AA||Höök, M||Ogren, S||Lindahl, U