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Chemical Compound Review

Chlorates     chlorate

Synonyms: Chlorate ion, Chlorate(1-), CHEBI:49709, HMDB02036, AC1L2XGT, ...
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Disease relevance of chlorate

  • Chlorate treatment of MM14 myoblasts abrogated the biological activity of acidic, basic, and Kaposi's sarcoma FGFs resulting in terminal differentiation [1].
  • The chlorate-resistant mutants of Escherichia coli are affected in the biosynthesis of the molybdenum cofactor and show pleiotropic loss of the activities of those enzymes which require the cofactor [2].
  • Thus on the basis of chlorate toxicity, it is possible to distinguish between amino acid substitutions that permit a low level of molybdopterin production and those mutations that completely abolish molybdopterin synthesis, most likely reflecting molybdopterin synthase activity per se [3].
  • Envelope glycoproteins synthesized in cells treated with chlorate failed to incorporate 35SO42-. However, HIV glycoproteins were still secreted from cells in the presence of chlorate, indicating that sulfation is not a requirement for secretion of envelope glycoproteins [4].
  • Decreased virulence of chlorate-resistant Salmonella typhimurium [5].

High impact information on chlorate

  • The CHL1 gene of Arabidopsis, which when mutated confers resistance to the herbicide chlorate and a decrease in nitrate uptake, was isolated and found to encode a protein with 12 putative membrane-spanning segments [6].
  • We have used chlorate as a metabolic inhibitor of sulphation, and report here that GlyCAM-1 has an additional requirement for sulphate [7].
  • Sera from subjects infected with a virulent invasive chlorate-resistant Shiga mutant thought to be "nontoxigenic" also contained antibody which was similarly restricted to the IgM fraction [8].
  • The interaction between L-selectin and leukocytes was protease sensitive and calcium dependent, and abolished by cell treatment with neuraminidase, chlorate, or O-sialoglycoprotein endopeptidase [9].
  • Addition of exogenous heparin to the chlorate-treated cells was able to restore WG activity [10].

Chemical compound and disease context of chlorate


Biological context of chlorate

  • This finding is consistent with the chlorate resistance phenotype of chl1 mutants [16].
  • Consistently, inhibitors such as p-nitrophenyl-beta-d-xylopyranoside and chlorate interfering with heparan sulfate proteoglycan biosynthesis reduced the total number of kininogen binding sites in a time- and concentration-dependent manner (up to 67%) [17].
  • Chlorate-sensitive mutants, all the result of amino acid substitutions, were shown to produce low levels of molybdopterin, and growth tests suggest that they have low levels of molybdoenzymes [3].
  • Finally, we demonstrate that undersulfation of proteoglycans by the chlorate treatment of chondrocytes significantly impaired growth response of the cells to fibroblast growth factor, suggesting a role for DTDST in endochondral bone formation [18].
  • The role of this post-translational modification on the cell attachment activity and secretion of a highly sulfated form of BSP isolated from a rat osteoblast-like cell line (UMR 106-01 BSP) was investigated by inhibiting sulfation with chlorate [19].

Anatomical context of chlorate

  • Treatment of skeletal muscle cells with chlorate, a reversible inhibitor of glycosaminoglycan sulfation, was used to examine the requirement of sulfated proteoglycans for FGF signalling [1].
  • Chlorate treatment did not affect the polarity of the expression of glypican in CaCo-2 cells, and transfectant MDCK cells expressed wild-type glypican and a syndecan-4/glypican chimera also in an essentially unpolarized fashion [20].
  • Here, we report the molecular characterization of a novel 2.5 kb human cDNA from MECA-79+ HEV-derived endothelial cells that encodes the target of chlorate, PAPS synthetase, a multifunctional enzyme containing domains for both ATP sulfurylase and adenosine-5'-phosphosulfate kinase [21].
  • Influence of chlorate on proteoglycan biosynthesis by cultured human fibroblasts [22].
  • Chlorate decreased the maximum binding of 125I-lipoprotein lipase to adipocytes by 4-fold, but no significant effects on the affinity constants were observed [23].

Associations of chlorate with other chemical compounds

  • At the same pH, the complete decomposition of 1 mole of chlorite yields 0.4 mole of chloride, 0.6 mole of chlorate, and 0.13 mole of oxygen [24].
  • The influence of chlorate, an inhibitor of sulfate adenylyltransferase, on biosynthesis and secretion of proteoglycans was investigated in cultured human skin fibroblasts [22].
  • Because of this lack of degradation of mannose-labeled P0 in the presence of chlorate in the crushed nerve, it is concluded that the absence of P0 sulfation does not result in a default mechanism for lysosomal delivery [25].
  • However, maximal digestion of the glycosaminoglycan chains of HSP with heparinase or culturing the cells in chlorate, an inhibitor of proteoglycan sulfation, did not affect the binding of 125I-RAP or of 125I-labeled, methylamine-activated alpha 2-macroglobulin [26].
  • Porphyrin-manganese(V)-oxo and porphyrin-manganese(IV)-oxo species were produced in organic solvents by laser flash photolysis (LFP) of the corresponding porphyrin-manganese(III) perchlorate and chlorate complexes, respectively, permitting direct kinetic studies [27].

Gene context of chlorate

  • From these data, we conclude that Arabidopsis has at least two functional nitrate reductase genes and that the NIA2 gene product accounts for the majority of the leaf nitrate reductase activity and chlorate sensitivity of Arabidopsis plants [28].
  • ECM produced in the presence of chlorate contained a nearly 10-fold less endogenous bFGF as compared to native ECM and exerted little or no mitogenic activity toward vascular EC and 3T3 fibroblasts [29].
  • We found that bFGF was able to bind, be internalized, and stimulate DNA synthesis in the absence of HSPG in a dose-dependent manner. bFGF bound to its receptors on chlorate-treated cells with a lower apparent affinity and no change in receptor number [30].
  • Heparin restored the high affinity binding of aFGF to chlorate-treated cells and completely abolished the high affinity binding of KGF [31].
  • Cytokine-stimulated endothelial cells also showed an increase in their potential to bind RANTES (CCL5); this was abrogated by chlorate blockade of sulphotransferase activity or by heparitinase cleavage of cell surface HS [32].

Analytical, diagnostic and therapeutic context of chlorate

  • 8. When foreign anions were exchanged for Cl- in the perfusion solution, the ten anaions smaller or equal to ClO3-, decreased the GABA depolarization by 50-90% and increased its time course 1.5-2.0 x control [33].
  • A colony that was invasive for HeLa cells and negative for the virG(icsA) gene by Southern blotting was grown anaerobically on plates containing chlorate for selection of resistant colonies that had lost the entire Shiga toxin gene [34].
  • Analysis of various compounds from different suppliers yielded delta37Cl values for chlorate samples near to +0.2/1000 (SMOC), but one has within-sample heterogeneity of 0.5/1000, possibly due to crystallization processes during manufacture [35].
  • Cells were labeled with [35S]SO4 with or without 10 mM chlorate, which inhibits sulfation by more than 90%, and media and cells were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, autoradiography, and immunoblotting using an antibody directed against the N-terminus of SgII [36].
  • Chlorate did not inhibit protein synthesis and did not exhibit any other toxic effects, even after prolonged treatment of cell cultures [37].


  1. Repression of myogenic differentiation by aFGF, bFGF, and K-FGF is dependent on cellular heparan sulfate. Olwin, B.B., Rapraeger, A. J. Cell Biol. (1992) [Pubmed]
  2. Molybdenum cofactor biosynthesis in Escherichia coli. Requirement of the chlB gene product for the formation of molybdopterin guanine dinucleotide. Johnson, J.L., Indermaur, L.W., Rajagopalan, K.V. J. Biol. Chem. (1991) [Pubmed]
  3. Eukaryotic molybdopterin synthase. Biochemical and molecular studies of Aspergillus nidulans cnxG and cnxH mutants. Unkles, S.E., Heck, I.S., Appleyard, M.V., Kinghorn, J.R. J. Biol. Chem. (1999) [Pubmed]
  4. Sulfation of the human immunodeficiency virus envelope glycoprotein. Bernstein, H.B., Compans, R.W. J. Virol. (1992) [Pubmed]
  5. Decreased virulence of chlorate-resistant Salmonella typhimurium. Speck, W.T., Wlodkowski, T.J., Rosenkranz, H.S. J. Infect. Dis. (1976) [Pubmed]
  6. The herbicide sensitivity gene CHL1 of Arabidopsis encodes a nitrate-inducible nitrate transporter. Tsay, Y.F., Schroeder, J.I., Feldmann, K.A., Crawford, N.M. Cell (1993) [Pubmed]
  7. Sulphation requirement for GlyCAM-1, an endothelial ligand for L-selectin. Imai, Y., Lasky, L.A., Rosen, S.D. Nature (1993) [Pubmed]
  8. Pathogenesis of shigella diarrhea. Serum anticytotoxin antibody response produced by toxigenic and nontoxigenic Shigella dysenteriae 1. Keusch, G.T., Jacewicz, M., Levine, M.M., Hornick, R.B., Kochwa, S. J. Clin. Invest. (1976) [Pubmed]
  9. P-selectin glycoprotein ligand 1 is a ligand for L-selectin on neutrophils, monocytes, and CD34+ hematopoietic progenitor cells. Spertini, O., Cordey, A.S., Monai, N., Giuffrè, L., Schapira, M. J. Cell Biol. (1996) [Pubmed]
  10. Glycosaminoglycans can modulate extracellular localization of the wingless protein and promote signal transduction. Reichsman, F., Smith, L., Cumberledge, S. J. Cell Biol. (1996) [Pubmed]
  11. Kinetic analysis of respiratory nitrate reductase from Escherichia coli K12. Morpeth, F.F., Boxer, D.H. Biochemistry (1985) [Pubmed]
  12. Biochemical studies on the catalysis of nitrosation by bacteria. Calmels, S., Ohshima, H., Rosenkranz, H., McCoy, E., Bartsch, H. Carcinogenesis (1987) [Pubmed]
  13. New enrichment method for isolation of pathogenic Yersinia enterocolitica serogroup O:3 from pork. Wauters, G., Goossens, V., Janssens, M., Vandepitte, J. Appl. Environ. Microbiol. (1988) [Pubmed]
  14. Gentamicin- and neomycin-resistant mutants of Escherichia coli K-12 cross-resistant to nitrofurans. Obaseiki-Ebor, E.E., Breeze, A.S. J. Antimicrob. Chemother. (1984) [Pubmed]
  15. Molybdenum cofactor (chlorate-resistant) mutants of Klebsiella pneumoniae M5al can use hypoxanthine as the sole nitrogen source. Garzón, A., Li, J., Flores, A., Casadesus, J., Stewart, V. J. Bacteriol. (1992) [Pubmed]
  16. CHL1 encodes a component of the low-affinity nitrate uptake system in Arabidopsis and shows cell type-specific expression in roots. Huang, N.C., Chiang, C.S., Crawford, N.M., Tsay, Y.F. Plant Cell (1996) [Pubmed]
  17. High molecular weight kininogen utilizes heparan sulfate proteoglycans for accumulation on endothelial cells. Renné, T., Dedio, J., David, G., Müller-Esterl, W. J. Biol. Chem. (2000) [Pubmed]
  18. Functional analysis of diastrophic dysplasia sulfate transporter. Its involvement in growth regulation of chondrocytes mediated by sulfated proteoglycans. Satoh, H., Susaki, M., Shukunami, C., Iyama, K., Negoro, T., Hiraki, Y. J. Biol. Chem. (1998) [Pubmed]
  19. Chlorate-induced inhibition of tyrosine sulfation on bone sialoprotein synthesized by a rat osteoblast-like cell line (UMR 106-01 BSP). Mintz, K.P., Fisher, L.W., Grzesik, W.J., Hascall, V.C., Midura, R.J. J. Biol. Chem. (1994) [Pubmed]
  20. Heparan sulfate expression in polarized epithelial cells: the apical sorting of glypican (GPI-anchored proteoglycan) is inversely related to its heparan sulfate content. Mertens, G., Van der Schueren, B., van den Berghe, H., David, G. J. Cell Biol. (1996) [Pubmed]
  21. Sulfation in high endothelial venules: cloning and expression of the human PAPS synthetase. Girard, J.P., Baekkevold, E.S., Amalric, F. FASEB J. (1998) [Pubmed]
  22. Influence of chlorate on proteoglycan biosynthesis by cultured human fibroblasts. Greve, H., Cully, Z., Blumberg, P., Kresse, H. J. Biol. Chem. (1988) [Pubmed]
  23. Effect of chlorate on the sulfation of lipoprotein lipase and heparan sulfate proteoglycans. Sulfation of heparan sulfate proteoglycans affects lipoprotein lipase degradation. Hoogewerf, A.J., Cisar, L.A., Evans, D.C., Bensadoun, A. J. Biol. Chem. (1991) [Pubmed]
  24. The reaction of chloroperoxidase with chlorite and chlorine dioxide. Shahangian, S., Hager, L.P. J. Biol. Chem. (1981) [Pubmed]
  25. Golgi sulfation of the oligosaccharide chain of P0 occurs in the presence of myelin assembly but not in its absence. Poduslo, J.F. J. Biol. Chem. (1990) [Pubmed]
  26. Exogenous receptor-associated protein binds to two distinct sites on human fibroblasts but does not bind to the glycosaminoglycan residues of heparan sulfate proteoglycans. Vassiliou, G., Stanley, K.K. J. Biol. Chem. (1994) [Pubmed]
  27. Laser flash photolysis generation and kinetic studies of porphyrin-manganese-oxo intermediates. Rate constants for oxidations effected by porphyrin-Mn(V)-oxo species and apparent disproportionation equilibrium constants for porphyrin-Mn(IV)-oxo species. Zhang, R., Horner, J.H., Newcomb, M. J. Am. Chem. Soc. (2005) [Pubmed]
  28. Identification of the Arabidopsis CHL3 gene as the nitrate reductase structural gene NIA2. Wilkinson, J.Q., Crawford, N.M. Plant Cell (1991) [Pubmed]
  29. Sulfate moieties in the subendothelial extracellular matrix are involved in basic fibroblast growth factor sequestration, dimerization, and stimulation of cell proliferation. Miao, H.Q., Ishai-Michaeli, R., Atzmon, R., Peretz, T., Vlodavsky, I. J. Biol. Chem. (1996) [Pubmed]
  30. Basic fibroblast growth factor binds its receptors, is internalized, and stimulates DNA synthesis in Balb/c3T3 cells in the absence of heparan sulfate. Fannon, M., Nugent, M.A. J. Biol. Chem. (1996) [Pubmed]
  31. Differential effect of cell-associated heparan sulfates on the binding of keratinocyte growth factor (KGF) and acidic fibroblast growth factor to the KGF receptor. Reich-Slotky, R., Bonneh-Barkay, D., Shaoul, E., Bluma, B., Svahn, C.M., Ron, D. J. Biol. Chem. (1994) [Pubmed]
  32. Endothelial inflammation: the role of differential expression of N-deacetylase/N-sulphotransferase enzymes in alteration of the immunological properties of heparan sulphate. Carter, N.M., Ali, S., Kirby, J.A. J. Cell. Sci. (2003) [Pubmed]
  33. Characterization and ionic basis of GABA-induced depolarizations recorded in vitro from cat primary afferent neurones. Gallagher, J.P., Higashi, H., Nishi, S. J. Physiol. (Lond.) (1978) [Pubmed]
  34. Construction, characterization, and animal testing of WRSd1, a Shigella dysenteriae 1 vaccine. Venkatesan, M.M., Hartman, A.B., Newland, J.W., Ivanova, V.S., Hale, T.L., McDonough, M., Butterton, J. Infect. Immun. (2002) [Pubmed]
  35. Methods for the stable isotopic analysis of chlorine in chlorate and perchlorate compounds. Ader, M., Coleman, M.L., Doyle, S.P., Stroud, M., Wakelin, D. Anal. Chem. (2001) [Pubmed]
  36. Prolactin and secretogranin-II, a marker for the regulated pathway, are secreted in parallel by pituitary GH4C1 cells. Hinkle, P.M., Scammell, J.G., Shanshala, E.D. Endocrinology (1992) [Pubmed]
  37. Chlorate--a potent inhibitor of protein sulfation in intact cells. Baeuerle, P.A., Huttner, W.B. Biochem. Biophys. Res. Commun. (1986) [Pubmed]
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