Metabolism of T-2 toxin by rat liver carboxylesterase.
The trichothecene T-2 toxin was rapidly hydrolyzed by rat liver microsomal fraction into HT-2 toxin which was the main metabolite. The metabolism was completely blocked by paraoxon, a serine esterase inhibitor, but not affected by EDTA or 4-hydroxy mercury benzoate, inhibitors of arylesterase and esterases containing SH-group in active site, respectively. Among the serine esterases carboxylesterase (EC 3.1.1.1), but not cholinesterase (EC 3.1.1.8) hydrolysed T-2 toxin to HT-2 toxin. Carboxylesterase activity from liver microsomes was separated into at least five different isoenzymes by isoelectric focusing, and only the isoenzyme of pI 5.4 was able to hydrolyse T-2 toxin to HT-2 toxin. The toxicity of T-2 toxin in mice was enhanced by pre-treatment with tri-o-cresyl phosphate (TOCP), a specific carboxylesterase inhibitor. This confirms the importance of carboxylesterase in detoxification of trichothecenes.
H
H
Johnsen
E
E
Odden
O
O
Lie
B A
BA
Johnsen
F
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Fonnum
D000818:Animals; D043182:Carboxylesterase; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism*; D007525:Isoelectric Focusing; D007527:Isoenzymes / Q000032:analysis; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D051381:Rats; D011919:Rats, Inbred Strains; D012717:Sesquiterpenes / Q000378:metabolism*; D013605:T-2 Toxin / Q000031:analogs & derivatives / Q000378:metabolism* / Q000633:toxicity; D014317:Tritolyl Phosphates / Q000494:pharmacology
D007527:Isoenzymes; D012717:Sesquiterpenes; D014317:Tritolyl Phosphates; D002265:Carboxylic Ester Hydrolases; D043182:Carboxylesterase; D013605:T-2 Toxin; C012351:HT-2 toxin; C025541:tri-o-cresyl phosphate