Rat liver aryl sulfotransferase-catalyzed sulfation and rearrangement of 9-fluorenone oxime.
The role of hepatic cytosolic aryl sulfotransferase (3'-phosphoadenylylsulfate:phenol sulfotransferase, EC 2.8.2.1) in the enzymic rearrangement of 9-fluorenone oxime to phenanthridone was investigated. 9-Fluorenone oxime was found to be an excellent substrate for a partially purified rat liver aryl sulfotransferase preparation. This compound was in fact superior to 2-naphthol, the standard assay substrate. This is the first reported observation of aryl oxime sulfation by the aryl sulfotransferases. 9-Fluorenone oxime sulfation exhibited pronounced substrate inhibition at high substrate concentrations. However, despite virtually complete conversion of 9-fluorenone oxime to the corresponding N-O-sulfate conjugate in enzyme incubation mixtures, only small amounts of rearrangement product were detected after long-term incubations. In addition, 9-fluorenone oxime-O-sulfonic acid was chemically synthesized and tested for stability. The results showed that rearrangement was pH-dependent and occurred slowly over several hours. It is therefore concluded that aryl sulfotransferase-catalyzed sulfation likely plays an important role in the in vitro and in vivo disposition of 9-fluorenone oxime. Moreover, sulfation facilitates the Beckmann-like conversion of 9-fluorenone oxime to phenanthridone. Sulfation alone, however, appears insufficient to account for all of the previously reported in vitro and in vivo rearrangement.
Mangold
J B
JB
Mangold
B L
BL
Spina
A
A
D000818:Animals; D015239:Arylsulfotransferase; D005449:Fluorenes / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008297:Male; D010616:Phenanthrenes / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013464:Sulfuric Acids / Q000378:metabolism; D013466:Sulfurtransferases / Q000378:metabolism*
D005449:Fluorenes; D010616:Phenanthrenes; D013464:Sulfuric Acids; C017876:fluorenone oxime; C040601:phenanthridone; D013466:Sulfurtransferases; D015239:Arylsulfotransferase