Studies on the biosynthesis of nicotinamide-adenine dinucleotide in the brain

Abstract

1. 1. The biosynthesis of NAD in the brain was investigated in vivo by following the metabolism of radioactive nicotinate, nicotinamide and their derivatives after injection into mice and rats. Although pyridine derivatives injected intraperioneally were incorporated efficiently into NAD in the liver and kidney, they could not readily penetrate into the brain, presumably due to the blood-brain barrier. 2. 2. Nicotinate injected into the cisternal cavity of rats was rapidly and efficiently converted to NAD in the brain by way of nicotinate ribonucleotide and deamido-NAD. 3. 3. Nicotinate ribonucleotide and deamido-NAD, administered in this way, were not directly utilized as precursors of NAD but were degraded to nicotinate ribonucleoside. The latter compound was phosphorylated again to the ribonucleotide and was converted to NAD. 4. 4. Nicotinate ribonucleoside was readily utilized as a precursor of NAD without prior degradation to nicotinate. 5. 5. Radioactive nicotinamide was also incorporated into NAD in the brain. This incorporation seems to be due to an exchange reaction with the nicotinamide moiety of NAD and does not represent de novo synthesis of NAD.