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Efficient synthesis of NAD+ is critical to maintaining cell viability in all organs of the body. However, little is known of the pathway(s) by which cells of the central nervous system produce NAD+. The aim of this study was to investigate the relationship, between tryptophan degradation via the kynurenine pathway (KP) and de novo NAD+ synthesis in human astrocytes, a major cell type within the brain. In this study we observed that inhibition of single enzymes of the KP resulted in significant decreases in NAD+ levels in astroglial cells after a 24 hr period. We also observed that astrocytes cultured in media deficient in tryptophan, nicotinic acid and nicotinamide resulted in a 50% decrease in NAD+ levels after 24 hrs. This decrease in NAD+ was partially restored by supplementation of the culture media with either tryptophan or kynurenine, or nicotinic acid or with supply of the salvage pathway precursor nicotinamide.


This article was originally published as:

Grant, R., Nguyen, S., & Guillemin, G. (2010). Kynurenine pathway metabolism is involved in the maintenance of the intracellular NAD+ concentration in human primary astrocytes. International Journal of Tryptophan Research, 3, 151–156. doi: 10.4137/IJTR.S7052

International Journal of Tryptophan Research may be accessed here.