+ NAD ,
+ NAD
recycling and brain metabolism
Caroline Rae1,2, Matthias Klugman2 & Benjamin D Rowlands1,2 Neuroscience Research Australia1 and School of Medical Sciences, The University of New South Wales2, Sydney, Australia
PROJECT BACKGROUND
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[email protected]
RESULTS
Nicotinamide adenine dinucleotide (NAD+), a coenzyme, is the major carrier of reducing equivalents. NAD+ availability reflects cell energy status, with low energy status equaling high availability of NAD+ vs NADH. It also reflects the amount of total NAD+ being consumed by silent information regulators (SIRTs) or other NAD+‐ases, and the amount of NAD+ being synthesized.
Addition of NAD+ increases NAD+ turnover, but total NAD+ remains constant
Addition of nicotinamide increases Nam but has little effect on NAD+
NMN has non‐ linear effects on NAD+ and Nam levels. NAD+ is a substrate for a range of NAD+ases which all have significant effects on metabolism. Nicotinamide is a known inhibitor of the NAD+ases Nicotinamide mononucleotide has been shown to have beneficial anti‐aging effects
AIMS Here, we examined the effects of supplying brain cortical tissue slices with different concentrations of NAD+, nicotinamide (Nam) or nicotinamide mononucleotide (NMN) on the metabolism of [1‐13C]D‐glucose and [1,2‐13C]acetate. We also examined the metabolic effects of inhibiting recycling via NAMPT using FK866.
Inhibiting NAMPT with FK866 slows NAD+ turnover
Figure 1: Total pool sizes of NAD+ and Nicotinamide in brain cortical tissue slices incubated for 1.5 h with 0.4 mM [1‐2‐13C]acetate and 5 mM [1‐13C]glucose Error bars represent standard deviations. Statistical significance indicated by * (P 0.5) Glu C4 P
