This reaction differs from general characteristics of phase II reactions.
METHYLATION
This reaction differs
from general characteristics of phase II reactions in several ways:
1. The metabolites formed are not
polar or water-soluble.
2. The metabolites, in a number
of instances, have equal or greater pharmacological activity than the parent
drug, e.g. morphine formed from normorphine.
3. The reaction is of lesser
importance in metabolism of xenobiotics. It is more important in the
biosynthesis (e.g. adrenaline, melatonin) and inactivation of endogenous amines
(e.g. noradrenaline, serotonin, histamine).
Methylation can be considered as intermediate of
phase I and phase II reactions. It can be called as a phase I reaction as it is
reverse of demethylation reaction and can be classed as a phase II reaction
because of its mechanism.
Methylation of substrates proceeds in two steps:
1. Synthesis of an activated coenzyme
S-adenosyl methionine (SAM), the donor of
methyl group, from L-methionine and ATP.
2. Transfer of the methyl group from SAM to
the substrate in presence of nonmicrosomal
enzyme methyl transferase.
Important methyl transferases that catalyse
methylation of xenobiotics are catechol-O-methyl transferase (COMT),
phenyl-O-methyl transferase (POMT), phenyl ethanolamine-N-methyl transferase
(PNMT), nonspecific transferases, etc.
Examples of substrates undergoing methylation are:
O-Methylation
Phenols e.g. morphine
Catechols e.g. -methyl dopa, L-DOPA, isoprenaline
N-Methylation
Primary aliphatic amines e.g.
norephedrine
Secondary alicyclic amines e.g.
normorphine
Aromatic heterocycles e.g.
nicotine, histamine
S-Methylation
Thiols e.g. propylthiouracil, 6-mercaptopurine
Related Topics
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