Metabolism of pyridinium precursors of pyridine nucleotides in perfused rat liver.

The uptake and metabolism of nicotinic acid, nicotinamide, and quinolinic acid at physiological concentrations by perfused rat liver have been studied. At a level of 400 mpmoles per liver, nicotinic acid was a more effective precursor of NAD than was nicotinamide. Labeled NAD in the liver reached maximum levels 10 min after nicotinic acid was added to the perfusate. When nicotinamide was the substrate, methylated compounds were the major products identified. The absence of labeled nicotinamide mononucleotide as well as nicotinic acid monoand dinucleotides precludes the possibility of choosing between the deamidation of nicotinamide or its direct incorporation into NAD. With large doses (1 mmole) of nicotinic acid the NAD level in the liver decreased, whereas NAD increased 2.5-fold during perfusion with nicotinamide (2 mmoles). Quinolinic acid was not a good precursor of NAD because of its limited uptake by the liver. During perfusion quinolinate transribosylase was released from the liver and catalyzed the decarboxylation of quinolinic acid as 5-phosphoribosyl-1-pyrophosphate became available.