Nicotinamide methylation and hepatic energy reserve: a study by liver perfusion in vitro

Background/Aims: The synthesis of pyridine nucleotides from nicotinamide requires adenosine triphosphate. In man when exogenous nicotinamide is poorly utilized in this synthesis, the excess follows a dissipative metabolic pathway and is excreted in urine as N-methylnicotinamide. In human cirrhosis N-methylnicotinamide serum levels are higher than normal, 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 depletion by metabolic stress. Methods: ''Stress'' was obtained by pre-washing with saline for 15 min before the perfusion with nutritive medium. Results: The adenosine triphosphate decrease in the stressed liver was 38% after pre-washing with saline and 80% at the end of nutritive perfusion, In control liver the corresponding decreases were 1% after pre-washing with nutritive medium and 65% at the end of perfusion with the same medium, The total nicotinamide adenine dinucleotide decreases were 44% and 56% in the stressed liver, and 19% and 52% in the control 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 and 66.40+/-13.17 for stressed liver (p