Liver nicotinamide methylation: N-methylnicotinamide-transferase expression in cirrhosis.

Nicotinamide (NA) methylation followed by urinary excretion of Nvmethylnicotinamide (NMN) has been shown to be increased in cirrhotic patients under basal conditions and after NA oral loading in spite of the well known derangement of overall methylation processes during hepatic failure . Such a finding could depend on induction and activity increase of the specific hepatic enzyme nicotinamide N-methyltransferase (NNMT). Therefore we studied by Western blot analysis with polyclonal anti-NNMT antibody the expression ofNNMT in liver biopsies of 13 normal control s (5M. mean age 53 y) and 37 patients with liver diseases. 25 (14M, mean age 43 y) with C virus chronic hepatitis and 12 (9M. mean age 43 y) with liver cirrhosis (8 Child A; 4 B). Statistical analysis was performed with ANOVA and post-test for linear trend. Hepatic NNMT expression (as a ratio to a reference value) was shown to progressively decrease. with a significant {p<0.05) linear trend, from normal liver (1.08:t0.46) to hepatitis (0.44:tO.l3) and. finally. to cirrhosis (0.17:t 0.11). The overall decrease of NNMT expression in cirrhotic versus nonn alliver amounted to 84%. These results may indicate that the increased NMN production in cirrhosis is dependent on a higher than normal turnover of NA to form NMN by NNMT in spite of its decreased hepatic tissue expression. The "hyperfunction" of this methylating pathway might playa protective role against the toxic effect of intracellular accumulation of NA resulting from the catabolic trend in cirrhotic patients