Physiology aspects of pyridine nucleotide regulation in mammals.

Tissue levels of NAD+ appear to be regulated primarily by the concentration of extracellular nicotinamide, which in turn is controlled by the liver in a hormone-sensitive manner. Hepatic regulation involves the conversion of excess serum nicotinamide to 'Storage NAD+' and inactive excretory products, and the replenishment of serum nicotinamide by the hydrolysis of 'Storage NAD+.' Tryptophan and nicotinic acid contribute to 'Storage NAD+,' and thus are additional sources of nicotinamide. In response to administered nicotinamide, there is a preferential utilization of ATP and PRPP (5-phosphorylribose-1-pyrophosphate) for the biosynthesis of NAD+. This biosynthetic priority, whose purpose appears to be the conservation of intracellular nicotinamide, may explain why nicotinamide inhibits RNA and DNA synthesis in regenerating tissues and why elevated nicotinamide levels are toxic to growing animals and to mammalian cells in culture.