Drug Elimination VI

Conjugations
The most important of phase II conjugation
reactions is glucuronidation. This
reaction does not proceed spontaneously,
but requires the activated form of
glucuronic acid, namely glucuronic acid
uridine diphosphate. Microsomal glucuronyl
transferases link the activated
glucuronic acid with an acceptor molecule.
When the latter is a phenol or alcohol,
an ether glucuronide will be
formed. In the case of carboxyl-bearing
molecules, an ester glucuronide is the
result. All of these are O-glucuronides.
Amines may form N-glucuronides that,
unlike O-glucuronides, are resistant to
bacterial !-glucuronidases.
Soluble cytoplasmic sulfotransferases
conjugate activated sulfate (3’-
phosphoadenine-5’-phosphosulfate)
with alcohols and phenols. The conjugates
are acids, as in the case of glucuronides.
In this respect, they differ from
conjugates formed by acetyltransferases
from activated acetate (acetylcoenzyme
A) and an alcohol or a phenol.
Acyltransferases are involved in the
conjugation of the amino acids glycine
or glutamine with carboxylic acids. In
these cases, an amide bond is formed
between the carboxyl groups of the acceptor
and the amino group of the donor
molecule (e.g., formation of salicyluric
acid from salicylic acid and glycine).
The acidic group of glycine or glutamine
remains free.