title: Molecular-size-dependent variations in the proportions of chains with high binding affinities for antithrombin in rat skin heparin proteoglycans.
abstract: Approximately half of all rat skin heparin proteoglycans have polysaccharide chains that have no sites with high binding affinity for antithrombin. The rest have chains with high-affinity antithrombin-binding-site densities ranging from zero to five sites per chain, with a high degree of variation. Proteoglycans vary in size because of diversity in the number of chains per molecule; the relationship between proteoglycan size and high-affinity antithrombin-binding-site density has not been studied previously. Polydisperse heparin proteoglycans from rat skin, labelled biosynthetically with 35S, were fractionated by gel filtration on Bio-Gel A-150m and arbitrarily divided into five fractions of decreasing average molecular size. Fractionation of these products on antithrombin-agarose showed that the proportion of proteoglycans with high affinity for antithrombin decreased from 39% to 25% as molecular size decreased. However, as the molecular size of high-affinity proteoglycans decreased, the proportion of their chains that had high affinity increased from 29% to 59%. Therefore molecular size is a significant factor in determining the proportion of high-affinity chains in heparin proteoglycans. A model of heparin biosynthesis is proposed in which areas of specific enzyme activity that control the synthesis of the antithrombin-binding-site sequence are sparsely and nonrandomly distributed on mast-cell Golgi membranes. It is postulated that the likelihood of a developing proteoglycan encountering one of these hypothetical areas is molecular-size-dependent.
authors.affiliation: Department of Physiology, University of Toronto, Ont., Canada.
authors.forename: A A
authors.initials: AA
authors.lastname: Horner
mesh_terms: D000818:Animals; D000991:Antithrombins / Q000378:metabolism*; D001665:Binding Sites; D002850:Chromatography, Gel; D006493:Heparin / Q000378:metabolism / Q000031:analogs & derivatives; D008297:Male; D008970:Molecular Weight; D011509:Proteoglycans / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012867:Skin / Q000378:metabolism*; D013462:Sulfur Radioisotopes
chemical_list: D000991:Antithrombins; D011509:Proteoglycans; D013462:Sulfur Radioisotopes; C036090:heparin proteoglycan; D006493:Heparin