Functional groups sulfate conjugation

Many drugs and metabolites are metabolized by conjugation with sulfate or glucuronic acid as described in Chapter 7. Sulfate conjugates can be hydrolyzed back to the alcohol or phenol. Glucuronide conjugates can involve a wider variety of functional groups and... 

If the foreign molecule already possesses a functional group suitable for a phase 2 reaction, a phase 1 reaction will be unnecessary. Thus, if phenol is administered to an animal, then it may immediately undergo a phase 2 reaction, such as conjugation with sulfate. Alternatively it may undergo another phase 1 type of reaction. The major types of reactions are shown in Table 4.2. 

Generally, therefore, the function of phase 1 reactions is to modify the structure of a xenobiotic so as to introduce a functional group suitable for conjugation with glucuronic acid, sulfate, or some other highly polar moiety, so making the entire molecule water soluble. 

Drugs and hormones that contain the phenolic functional group are metabolised by conjugation to a sulfate group (a process called sulfation). Examples of compounds metabolised in this way include the neurotransmitter noradrenaline (norepinephrine) as well as hormones such as... 

Sulfation is another common form of conjugation predominately found with phenolic compounds however, sulfate esters can also be formed with alcohols, aryl-amines, and N-hydroxy compounds. Sulfation involves the transfer of S03 from 3 -phosphoadenosine-5 -phosphosulfate (PAPS) to one of the above-mentioned functional groups by an enzyme-catalyzed reaction involving the cytosolic enzymes (sulfotransferases), as illustrated in Fig. 24 [11]. It is common to find phenolic compounds that are metabolized by both sulfation and glucuronidation, as they are often competing pathways. However, sulfation has a significant limitation... 

The POPs we consider in this chapter are non-ionizable, and largely non-polar. These characteristics make them poorly soluble in water and thus hydrophobic. Introduction of an ionizable functional group, such as a sulfate or conjugate as occurs with metabolism, greatly increases the water solubility of hydrophobic compounds (due to hydration of the ionizable moieties), and such modified compounds are rapidly... 

Conjugation of 0-, N- and S-contalnlng functional groups with sulfate Is very common In animal systems. Sulfate Is transferred from adenosine 3 -phosphate-5 -sulfatophosphate (PAPS) by a variety of transfer enzymes. The mechanisms for sulfation of xenobiotics (74,75) and the chemistry of sulfate esters and related compounds and the synthesis of these have been reviewed (75-77). Syntheses of 0-, N- and S-sulfate conjugates of xenobiotics may be carried out by the methods described below. 

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