Molecular-size-dependent variations in the proportions of chains with high binding affinities for antithrombin in rat skin heparin proteoglycans.
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.
Horner
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AA
Department of Physiology, University of Toronto, Ont., Canada.
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
D000991:Antithrombins; D011509:Proteoglycans; D013462:Sulfur Radioisotopes; C036090:heparin proteoglycan; D006493:Heparin