Nicotinamide methylation and hepatic energy reserve.

In liver diseases the reduction of hepatic energy reserve may affect many metabolic pathways that require ATPR e.g. the synthesis of pyridine nucleotides from nicotinamide (NAM). When exogenous NAM is poorly utilized in this synthesis, it follows a dissipative metabolic pathway and is excreted in urine as N-methyinicotinamide (NMN). Recently we reported a significant increase of NMN production and excretion in cirrhotic patients in basal condition and after NAM oral load. The aim of this study was to verify NAM methylation in relation to liver content of ATP and glycogen during rat liver in vitro perfusion with or without metabolic stress. The stress was obtained by a 15 min delay in Krebs medium perfusion of isolated liver. The metabolic stress significantly reduced the liver content of ATP The production of NMN in the stressed rat liver is significantly higher than in normal liver. The NAM liver methylation is inversely related to ATP (r = -0.74; p < 0.01) and glycogen (r = -0.53; p < 0.05) levels. In conclusion this study suggests that the increase of NMN production in cirrhotic patients may depend on the energy crisis of liver cell