Alan A. Horner

Demonstration of endogenous heparin in rat blood.

Dr. Lindahl has referred to my concept of macromolecular heparin as a multichain, whose structural integrity depends on a polysaccharide core. In 1971, I postulated that macromolecular heparin must be depolymerized to become biologically active (6). Later, I found that macromolecular heparin is a potent inhibitor of heart lipoprotein lipase (LPL) in vitro (7). Injected macromolecular heparin has a relatively low potency as an initiator of LPL activity in the blood. This activity appears in the blood rather slowly, compared with that of low-molecular-weight heparin (i.e., commercial heparin or enzymatically depolymerized macromolecular heparin) (7). These facts support the concept that depolymerization precedes the release of biologically active heparin from the mast cells. Endogenous heparin in the blood should therefore be of low molecular weight, and I would now like to demonstrate that this is so.

Identification and Quantification of Tissue Heparin by Microelectrophoresis: A Critique

In 1968, Jaques, Ballieux, Dietrich, and Kavanagh described the use of microelectrophoresis in agarose gel at a pH of 8.6 to quantitate heparin in tissues (2). Using this method, Jaques and Debnath (3) found high concentrations of heparin in rat tissues in which other workers had previously failed to detect any. From their data, which showed considerable heparin in tissues containing very few mast cells, they postulated the existence of “non-mast-cell heparin.” Jaques and Roy (4) used the same method to demonstrate high heparin concentrations in blood vessels, especially aorta, in which other workers had previously failed to detect it by accepted biochemical techniques (9).

THE METABOLISM OF MACROMOLECULAR HEPARIN

This paper presents evidence that macromolecular heparin is a unique protease-resistant proteoglycan. It is comprised of heparin chains, which are much larger than those of commercial heparin, linked through alkali-labile glycosidic linkages involving the hydroxyl groups of serine residues to a peptide core comprised entirely of equimolar proportions of serine and glycine.