Conjugation With Sulphate Moieties

CONJUGATION WITH SULPHATE MOIETIES

Sulphation is similar to glucuronidation but it is catalysed by nonmicrosomal enzymes and occurs less commonly as the moiety that transfers sulphate to the substrate is easily depleted. This process is thus, easily saturable in comparison to glucuronidation.

^·            Sulphation is dominant at low substrate concentration, whereas

^·            Glucuronidation is dominant at high substrate concentration.

Like glucuronidation, sulphation also occurs in 2 steps:

1. Synthesis of an activated coenzyme 3'-phosphoadenosine-5'- phosphosulphate (PAPS) which acts as a donor of sulphate to the substrate. This also occurs in two steps —

(a) An initial interaction between the sulphate and the adenosine triphosphate (ATP) to yield adenosine-5'-phosphosulphate (APS), followed by

(b) Activation of APS to PAPS.

2. Transfer of sulphate group from PAPS to the substrate RXH in presence of enzyme sulphotransferase (sulphokinase) and subsequent liberation of 3'-phosphoadenosine-5'-phosphate (PAP).

The steps are summarized in the equations below:

where X = O, NH

Functional groups capable of forming sulphate conjugates include phenols, alcohols, arylamines, N-hydroxylamines and N-hydroxyamides. The reaction product is a sulphate ester, also called as ethereal sulphate.

Examples of compounds undergoing sulphation are:

Phenols e.g. paracetamol, salbutamol

Alcohols e.g. aliphatic alcohols C-1 to C-5

Arylamines e.g. aniline.

Sulphoconjugates can be tissue reactive, e.g. the O-sulphate conjugate of N-hydroxy phenacetin covalently binds to hepatic and renal tissues.

Endogenous substances can also undergo sulphation, e.g. steroids, biologic amines, etc.