Abstract
With the exception of hyaluronic acid, all glycosaminoglycans are O-sulfated. Heparins and heparan sulfates are, in addition, N-sulfated on many of their glucosamine residues. Other naturally occurring structures are also sulfated. For example, some proteins contain sulfotyrosine residues (1), and some complex lipids are O-sulfated. In addition, certain N-linked oligosaccharides are sulfated (2). In all of these cases, the enzymes that add sulfate residues to these structures utilize 3′-phosphoadenosine5′-phosphosulfate (PAPS) as the sulfate donor. If PAPS cannot be synthesized, these biological sulfation reactions will not proceed. Chlorate is a competitive inhibitor of PAPS synthesis and, as such, can block all sulfation reactions.
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References
Mintz, K. P., Fisher, L. W., Grzesik, W. J., Hascall, V. C., and Midura, R. J. (1994) Chlorateinduced inhibition of tyrosine sulfation on bone sialoprotein synthesized by a rat osteoblastlike cell line (UMR 106-01 BSP). J. Biol. Chem. 269, 4845–4852.
Baenziger, J. U., Kumar, S., Bradbeck, R. M., Smith, P. L., and Beranek, M. C. (1992) Circulatory half-life but not interaction with the lutropin/chorionic gonadotropin receptor is modulated by sulfation of bovine lutropin oligosaccharides. Proc. Natl. Acad. Sci. (USA) 89, 334–338.
Lyle, S., Stanczak, J., Ng, K., and Schwartz, N. B. (1994) Rat chondrosarcoma ATP sulfurylase and adenosine 5′-phosphosulfate kinase reside on a single bifunctional protein, Biochemistry 33, 5920–5925.
Besset, S., Vincourt, J.-B., Amalric, F., and Girard, J. P. (2000) Nuclear localization of PAPS synthetase 1: a sulfate activation pathway in the nucleus of eukaryotic cells. FASEB J. 14, 345–354.
Safaiyan, F., Lindahl, U., and Salmivirta, M. (1998) Selective reduction of 6-O-sulfation in heparan sulfate from transformed mammary epithelial cells. Eur. J. Biochem. 252, 576–582.
Baeuerle, P. A. and Huttner, W. B. (1986) Chlorate-a potent inhibitor of protein sulfation in intact cells. Biochem. Biophys. Res. Commun. 141, 870–877.
Greve, H., Cully, Z., Brumborg, P., and Kresse, H. (1988) Influence of chlorate on proteoglycan biosynthesis by cultured human fibroblasts. J. Biol. Chem. 263, 128,865–128,892.
Humphries, D. E. and Silbert, J. E. (1988) Chlorate: a reversible inhibitor of proteoglycan sulfation. Biochem. Biophys. Res. Commun. 14, 365–371.
Keller, K. M., Brauer, P. B., and Keller, J. M. (1989) Modulation of cell surface heparan sulfate structure by growth of cells in the presence of chlorate. Biochemistry 28, 8100–8107.
Hoogewerf, A. J., Cisar, L. A., Evans, D. C., and Bensadoun, A. (1991) Effect of chlorate on the sulfation of lipoprotein lipase and heparan sulfate proteoglycans: sulfation of heparan sulfate proteoglycans affect lipoprotein lipase degradation. J. Biol. Chem. 266, 16,564–16,571.
Yayon, A., Klagsbrun, M., Esko, J. D., Leder, P., and Ornitz, D. M. (1991) Cell surface, heparin-like molecules are required for binding of basic fibroblast growth factor to its high affinity receptor. Cell 64, 841–848.
Ornitz, D. M., Yayon, A., Flanagan, J. G., Svahn, C. M., Levi, E., and Leder, P. (1992) Heparin is required for cell-free binding of basic fibroblast growth factor to a soluble receptor and for mitogenesis in whole cells. Mol. Cell. Biol. 12, 240–247.
Ishihara, M., Tyrrell, D. J., Stauber, G. B., Brown, S., Cousens, L. S., and Stack, R. J. (1993) Preparation of affinity-fractionated, heparin-derived oligosaccharides and their effects on selected biological activities mediated by basic fibroblast growth factor. J. Biol. Chem. 268, 4675–4683.
Ji, Z.-S., Lauer, S. J., Fazio, S., Bensadoun, A., Taylor, J. M., and Mahley, R. W. (1994) Enhanced binding and uptake of remnant lipoproteins by hepatic lipase-secreting hepatoma cells in culture. J. Biol. Chem. 269, 13,429–13,436.
Berryman, D. E., and Bensadoun, A. (1995) Heparan sulfate proteoglycans are primarily responsible for the maintenance of enzyme activity, binding, and degradation of lipoprotein lipase in Chinese hamster ovary cells. J. Biol. Chem. 270, 24,525–24,531.
Liu, G., Bengtsson-Olivecrona, G., and Olivecrona, T. (1993) Assembly of lipoprotein lipase in perfused guinea pig hearts. Biochem. J. 292, 277–282.
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© 2001 Humana Press Inc., Totowa, NJ
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Edward Conrad, H. (2001). Inhibition of Heparan Sulfate Synthesis by Chlorate. In: Iozzo, R.V. (eds) Proteoglycan Protocols. Methods in Molecular Biology™, vol 171. Humana Press. https://doi.org/10.1385/1-59259-209-0:325
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DOI: https://doi.org/10.1385/1-59259-209-0:325
Publisher Name: Humana Press
Print ISBN: 978-0-89603-759-5
Online ISBN: 978-1-59259-209-8
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