Purpose: The possible mechanisms of increased arylamine N-methyl- transferase (AMT) activity in cholestatic rat livers and serum were studied. Methods: Rats were divided into eight groups: rats receiving a sham operation, rats with a bile duct
obstruction (BDO) alone (BDO group), rats with a BDO plus taurocholic acid (TCA) injection (BDO plus TCA group), rats with a BDO plus tauroursodeoxycholic acid (TUDCA) injection (BDO plus TUDCA group), rats receiving a choledocho-caval shunt
(CCS)
operation (CCS groups), rats receiving a CCS operation plus TCA injection (CCS plus TCA group), and rats receiving a CCS operation plus TUDCA injection (CCS plus TUDCA group). The AMT activities in the serum and in the hepatic subcellular
fractions
isolated from the above experimental rats were determined. The values of Km and Vmax in this hepatic enzyme were measured. Results: The activities of liver mitochondrial and microsomal AMTs as well as the Vmax values of AMT, were found to be
increased
significantly in both the CCS plus TCA group and the BDO plus TCA group compared with the CCS and BDO groups. On the other hand, the values of Km of hepatic subcellular AMT was the same in all experimental groups. The serum AMT activity increased
significantly in both the CCS plus TCA group and the BDO plus TCA group compared with control the CCS and BDO group. However, these serum and hepatic enzyme activities were the same in both the CCS plus TUDCA group and the BDO plus TUDCA group.
Conclusion: The above results suggest that TCA stimulates the biosynthesis of AMT in the liver. Also, the elevated AMT activity in the serum is thought to be caused by an increase in the membrane permeability of hepatocytes from liver cell
necrosis
caused by TCA.
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