Popis: |
The foregoing pages presented a substantial body of data that established that sulfotransferase conjugation can transform many xenobiotics into agents that can modify cellular macromolecules. However, activation by sulfation is rarely the only metabolic pathway that is open to these compounds; other pathways can become more important in response to a variety of factors. This metabolic switching can be produced by substrate concentration, cofactor availability, kinetic factors that dictate the velocity of the various possible conjugation reactions, and, in some cases, competition between Phase-I and Phase-II metabolism. Also, it is important to realize that demonstration of activation by sulfate ester formation in vitro does not necessarily mean that a similar activation process will occur in vivo. Experience also teaches that argument by analogy can be very misleading in the case of sulfate activation. Small structural differences can upset the delicate balance between sulfate activation and the various other competing pathways. Nevertheless, sulfation is an important mechanism by which a number of chemicals are transformed to their activated forms. |