Abstract | OBJECTIVES:
Nicotinamide methylation followed by urinary excretion of N-methylnicotinamide increases in cirrhotic patients, despite the derangement of the overall methylation processes in liver disease. The rise in N-methylnicotinamide could depend, at least in part, on a reduced transformation of this molecule into 2-pyridone-5-carboxamide. The aim of this study was to investigate this hypothesis. METHODS: RESULTS:
N-methylnicotinamide serum levels increased significantly (p < 0.01) in cirrhotic patients compared to controls, both as basal values (0.43 +/- 0.07 nmol/ml; 0.15 +/- 0.01) and as area under the curve 5 h after a nicotinamide load (cirrhotics: 562.4 +/- 50.5 nmol/ml x min; controls: 314.4 +/- 23.8). Twenty-four-hour urinary excretion of N-methylnicotinamide and 2-pyridone-5-carboxamide was also significantly (p < 0.05) increased in cirrhotic patients versus controls, both in basal conditions ( N-methylnicotinamide: 82.0 +/- 8.4 micromol, 48.8 +/- 4.8; 2-pyridone-5-carboxamide: 129.3 +/- 23.0, 64.6 +/- 9.8) and after a nicotinamide oral load ( N-methylnicotinamide: 290.1 +/- 23.1, 180.8 +/- 7.4; 2-pyridone-5-carboxamide: 694.7 +/- 32.5, 391.0 +/- 21.9). Moreover, 24 h N-methylnicotinamide/2-pyridone-5-carboxamide ratio was similar in patients and controls (basal: 0.78 +/- 0.39, 0.90 +/- 0.51; load: 0.42 +/- 0.11, 0.48 +/- 0.16). CONCLUSIONS: In cirrhotic patients nicotinamide methylation is increased, as shown by the rise in urinary N-methylnicotinamide and 2-pyridone-5-carboxamide that is concurrent and proportional (constant 24-h metabolite ratio). The hyperfunction of this methylating pathway might play a protective role against the toxic effect of intracellular accumulation of nicotinamide deriving from the catabolic state of cirrhosis.
|
Authors | R Pumpo, G Sarnelli, A Spinella, G Budillon, R Cuomo |
Journal | The American journal of gastroenterology
(Am J Gastroenterol)
Vol. 96
Issue 4
Pg. 1183-7
(Apr 2001)
ISSN: 0002-9270 [Print] United States |
PMID | 11316167
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Niacinamide
- N'-methyl-2-pyridone-5-carboxamide
- N-methylnicotinamide
|
Topics |
- Adult
- Female
- Humans
- Liver Cirrhosis
(metabolism)
- Male
- Middle Aged
- Niacinamide
(analogs & derivatives, biosynthesis, metabolism)
|