Methylation catalyzed by
methyltransferases is a major metabolic pathway for an inactivation of some
catecholamines,
niacinamide as well as aliphatic sulfhydryl drugs and toxic
hydrogen sulfides. To investigate the effects of
obstructive jaundice in an animal model, common bile duct
ligation (CBDL) was performed in the rat and
enzyme activities of
S-adenosyl-L-methionine-dependent
arylamine N-methyltransferase and
thiol methyltransferase were examined in liver cell fractions and serum for a period of 42 d after CBDL. Both mitochondrial and microsomal
arylamine N-methyltransferase showed significant increases in their activities between the 1st through the 7th day (P < or = 0.05 to 0.001), and between the 1st through the 28th day (P < or = 0.01 to 0.001) post-
ligation, although the cytosolic
arylamine N-methyltransferase activity did not show a significant change compared to the activities from the
sham-operated control. The mitochondrial as well as microsomal
thiol methyltransferase showed significant increases in their activities between the 1st through the 28th day (P < or = 0.05 to 0.01 and P < or = 0.01 to 0.001, respectively) post-
ligation, although the cytosolic
thiol methyltransferase activity did not show a significant change compared to the activities from the
sham-operated control.
Arylamine N-methyltransferase and
thiol methyltransferase in the serum from cholestatic rats also showed significant increases in their activities between the 1st through 28th day (P < or = 0.01 to 0.001), and between the 0.5th through the 42nd day (P < or = 0.05 to 0.001) post-
ligation compared to the
sham-operated control, respectively.
Enzyme kinetic parameters (Km and Vmax) of hepatic membrane-bound
arylamine N-methyltransferase and
thiol methyltransferase were analyzed with the preparation from the 7th day post-
ligation, using
tryptamine or 4-chlorothiophenol as substrates and S-Adenosyl-L-[methyl-3H]
methionine as co-substrate. The results indicate that although the Km values were about the same as the
sham-operated control, the Vmax values of both
enzymes increased significantly (P < or = 0.01 and 0.001, respectively). These results suggest that the biosynthesis of
arylamine N-methyltransferase and
thiol methyltransferase have been induced in response to
obstructive jaundice.