PHASE II reactions
Glucuronide conjugation
 Sulphate conjugation
 Acetylation and Acylation
 Amino acid conjugation
 Glutathion conjugation

PHASE II reactions
CONJUGATIONS
• -OH,
-SH, -COOH, -CONH with glucuronic
acid to give glucuronides
• -OH with sulphate to give sulphates
• -NH2, -CONH2, aminoacids, sulpha drugs
with acetyl- to give acetylated derivatives
• -halo, -nitrate, epoxide, sulphate with
glutathione to give glutathione conjugates
all tend to be less lipid soluble and therefore better
excreted (less well reabsorbed)
Glucuronide conjugation
. liver enzymes catalyze the synthesis of “Uridine diphosphate
glucouronic acid” (UDPGA)
(UDPGA)
(UDPG)
(B-Glucoronide conj)
Therefore there is inversion of configration
(from alpha into beta B-Glucoronide conj).
The mechanism of glucuronidation



Nucleophilic substitution with inversion of
configuration, α-D-glucuronic acid in UDPGA
forming β-D-glucuronides
The functional groups able to undergo
glucuronidation are classified as O-, N-, Sand C- glucuronides.
Glucuronic acidc can also act as
nucleophile,attacking an electropostive
carbonyl carbon to yield the common class of
Acyl glucuronides.
O-Glucuronidation
.(Naproxen)
This class is most frequently involved in reactive
metabolite formation.
Morphine is conjugated on its phenolic and secondary alcohol groups
to form the 3-O-glucuronide ( a weak antagonist) and 6-O-(a strong
opiate agonist
N-Glucuronidation

Carboxamides, sulfonamides, various amines
Desimpramine
.Desmethylimpramine
S-Glucuronidation
c-Glucuronidation

Carbon glucuronide