Biliary excretion of nicotinamide riboside: A possible role in the regulation of hepatic pyridine nucleotide dynamics

Abstract

Female rats fed approximately 5 mg/day/kg of body wt of nicotinic acid- 14C excreted 10 per cent of the daily ingested label in bile and 57 per cent in urine. Approximately two-thirds of the label in bile was present as nicotinamide riboside. Chemical analysis of nicotinamide riboside indicates that about 7 μmoles/day/kg of body wt are excreted into bile. Chemical and radiochemical analyses both indicate that biliary nicotinamide riboside excretion may account for a major fraction of the hepatic pyridine nucleotide turnover. Nicotinamide riboside was not detected in urine, while 1-methylnicotinamide was present in urine but not in bile. Of the daily dietary intake, 6.7 per cent was excreted in bile as nicotinamide riboside while 19.6 per cent was excreted in urine as 1-methylnicotinamide. After intra peritoneal administration of 150 mg/kg of nicotinic acid or 500 mg/kg of nicotinamide, the hepatic NAD + content increases 2 to 4-fold, accompanied by a marked increase in the turnover of this newly formed NAD +. The biliary excretion of nicotinamide riboside increases up to ten times the normal rate during this period of increased hepatic NAD + turnover. The nicotinamide riboside excretion appears to be related to the elevation of NAD + and is independent of whether nicotinic acid or nicotinamide is used as the precursor. Comparison of the biliary nicotinamide riboside excretion with published values for the urinary excretion of NAD + metabolites during a similar hepatic NAD + increase indicates that the biliary route may be a major pathway for the elimination of hepatic NAD + metabolites. 1-Methylnicotinamide was not found in bile unless very large intravenous doses were given to animals with ligated renal pedicles. The possible role of the biliary system in pyridine nucleotide dynamics and the possible relation of biliary nicotinamide riboside excretion to the secretion of other organic cations into bile are discussed.