Conjugation with sulphate moiety

1. Biopharmaceutics and Pharmacokinetics
Topic: Conjugation with Sulphate Moiety
Prepared By: Bhagyashree Dilip Rajput
Cclass: T. Y. B. Pharm
Division: B
Roll No: 111
College: Shri. D.D. Vispute College of Pharmacy and Research Center,
Vichumbe, Panvel.

2. CONJUGATION WITH SULPHATE MOIETIES
• It is one of the Phase II reaction of Drug Biotransformation.
• 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.

3. • 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 —
• An initial interaction between the sulphate and the adenosine
triphosphate (ATP) to yield adenosine-5'-phosphosulphate (APS),
followed by
• Activation of APS to PAPS

4. 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

5. 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.

6. • 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.

7. Thank You