Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.6.1 (sulfatase)
 3,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diphosphonates are known to inhibit bone resorption in tissue culture and in experimental animals. This effect may be due to their ability to inhibit the dissolution of hydroxyapatite crystals, but other mechanisms may be important. Since lysosomal enzymes have implicated in the process of bone resorption, we have examined the effect of several phosphonates and of a polyphosphate (P20,2) on lysosomal hydrolases derived from rat liver and rat bone. Dichloromethylene diphosphonate strongly inhibited acid beta-glycerophosphatase (EC 3.1.3.2) and acid p-nitrophenyl phosphatase (EC 3.1.3.2) and to a lesser degree (in descending order) acid pyrophosphatase (EC 3.1.3.-), arylsulfatase A (EC 3.1.6.1), deoxyribonuclease II(EC 3.1.4.6) and phosphoprotein phosphatase (EC 3.1.3.16) of rat liver. Inhibition of acid p-nitrophenyl phosphatase and arylsulfatase A was competitive. Ethane-1-hydroxy-1, 1-diphosphonate did not inhibit any of these enzymes, except at high concentrations. Neither dichloromethylene diphosphonate nor ethane-1-hydroxy-1, 1-diphosphonate had any effect on beta-glucuronidase (EC 3.2.1.31), arylesterase (EC 3.1.1.2) and cathepsin D (EC 3.4.23.5). Of several other phosphonates tested only undec-10-ene-1-hydroxy-1, 1-diphosphonic acid inhibited acid p-nitrophenyl phosphatase strongly, the polyphosphate (P20, I) had little effect. Acid p-nitrophenyl phosphatase in rat calvaria extract behaved in the same way as the liver enzyme and was also strongly inhibited by dichloromethylene diphosphonate, but not by ethane-1-hydroxy-1, 1-diphosphonate. It is suggested that the inhibition of bone resorption by dichloromethylene diphosphonate might be due in part to a direct effect of this diphosphonate on lysosomal hydrolases.
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PMID:The effect of several diphosphonates on acid phosphohydrolases and other lysosomal enzymes. 17 70

Previous results have suggested that key intermediates in the activation of 2-nitrotoluene and 2,6-dinitrotoluene are 2-aminobenzyl alcohol and 2-amino-6-nitrobenzyl alcohol, respectively. In order to determine the metabolic pathway(s) involved in the activation steps, calf thymus DNA and [14C]-2-aminobenzyl alcohol or [14C]-2-amino-6-nitrobenzyl alcohol were incubated with male Fischer-344 rat hepatic cytosol and PAPS, microsomes and NADPH, or microsomes and cytosol with PAPS, NADPH, and acetyl coenzyme A. DNA was isolated and analyzed for radiolabel bound covalently. Analysis of the incubations containing [14C]-2-aminobenzyl alcohol revealed radiolabel bound covalently to DNA, as well as one major metabolite labile in both sulfatase and acid. The appearance of each required the presence of PAPS and cytosol and was inhibited by the sulfotransferase inhibitor 2,6-dichloro-4-nitrophenol. Neither NADPH nor acetyl coenzyme A played a role in the generation of detectable 14C bound to nucleic acids. 2-Amino-6-nitrobenzyl alcohol was converted to metabolites capable of binding to calf thymus DNA when incubated with cytosol and PAPS or with microsomes and NADPH. However, when cytosol and microsomes were incubated together, activation of 2-amino-6-nitrobenzyl alcohol appeared to require only PAPS, suggesting a minor role for NADPH-dependent enzymes in its activation. The results suggest that the metabolite of 2-nitrotoluene responsible for binding covalently to DNA is 2-aminobenzyl sulfate. There may be more than one pathway involved in the formation of metabolite(s) of 2,6-dinitrotoluene that bind covalently to DNA.
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PMID:In vitro activation of 2-aminobenzyl alcohol and 2-amino-6-nitrobenzyl alcohol, metabolites of 2-nitrotoluene and 2,6-dinitrotoluene. 251 19