Nicotinamide methylation and hepatic energy reserve: a study by liver perfusion in vitro.
OBJECTIVE
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<0.001). Liver adenosine triphosphate was inversely related to N-methylnicotinamide production (r=0.93; p<0.001).


CONCLUSIONS
These data suggest that nicotinamide methylation may be enhanced when there is hepatic adenosine triphosphate decrease and energy failure induced by hypoxia or metabolic stress, similar to that obtained in vitro by saline washing before perfusion with nutritive medium. This study shows that the evaluation of N-methylnicotinamide production in man (before and after nicotinamide load) might be useful to explore the energy state of diseased liver.
Cuomo
R
R
Cattedra di Gastroenterologia, Facoltà di Medicina, Università degli Studi di Napoli Federico II, Italy.
Pumpo
R
R
Sarnelli
G
G
Capuano
G
G
Budillon
G
G
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D008745:Methylation; D009243:NAD / Q000378:metabolism; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley
D009243:NAD; D009536:Niacinamide; D000255:Adenosine Triphosphate; C008472:N-methylnicotinamide