NICOTINAMIDE METHYLATION AND HEPATIC ENERGY RESERVE - A STUDY BY LIVER PERFUSION IN-VITRO

Background/Aims: The synthesis of pyridine nucleotides from nicotinami de requires adenosine triphosphate. In man when exogenous nicotinamide is poorly utilized in this synthesis, the excess follows a dissipativ e metabolic pathway and is excreted in urine as N-methylnicotinamide. In human cirrhosis N-methylnicotinamide serum levels are higher than n ormal, in basal condition and after nicotinamide oral load, The aim of this study was to verify N-methylnicotinamide production in relation to hepatic content of adenosine triphosphate during in vitro perfusion of rat liver, in normal conditions and after adenosine triphosphate d epletion by metabolic stress. Methods: ''Stress'' was obtained by pre- washing with saline for 15 min before the perfusion with nutritive med ium. Results: The adenosine triphosphate decrease in the stressed live r was 38% after pre-washing with saline and 80% at the end of nutritiv e perfusion, In control liver the corresponding decreases were 1% afte r pre-washing with nutritive medium and 65% at the end of perfusion wi th the same medium, The total nicotinamide adenine dinucleotide decrea ses were 44% and 56% in the stressed liver, and 19% and 52% in the con trol liver, The output levels of N-methylnicotinamide at 90 min of rat liver nutritive perfusion were 31.50+/-4.72 nmol/g for normal liver a nd 66.40+/-13.17 for stressed liver (p<0.001). Liver adenosine triphos phate was inversely related to N-methylnicotinamide production (r=0.93 ; p<0.001). Conclusions: These data suggest that nicotinamide methylat ion may be enhanced when there is hepatic adenosine triphosphate decre ase and energy failure induced by hypoxia or metabolic stress, similar to that obtained in vitro by saline washing before perfusion with nut ritive medium, This study shows that the evaluation of N-methylnicotin amide production in man (before and after nicotinamide load) might be useful to explore the energy state of diseased liver.