Quantitation of NAD+ biosynthesis from the salvage pathway in Saccharomyces cerevisiae

Yeast. 2009 Jul;26(7):363-9. doi: 10.1002/yea.1671.

Abstract

Nicotinamide adenine dinucleotide (NAD+) is synthesized via two major pathways in prokaryotic and eukaryotic systems: the de novo biosynthesis pathway from tryptophan precursors, or the salvage biosynthesis pathway from either extracellular nicotinic acid or various intracellular NAD+ decomposition products. NAD+ biosynthesis via the salvage pathway has been linked to an increase in yeast replicative lifespan under calorie restriction (CR). However, the relative contribution of each pathway to NAD+ biosynthesis under both normal and CR conditions is not known. Here, we have performed lifespan, NAD+ and NADH (the reduced form of NAD+) analyses on BY4742 wild-type, NAD+ salvage pathway knockout (npt1Delta) and NAD+ de novo pathway knockout (qpt1Delta) yeast strains cultured in media containing either 2% glucose (normal growth) or 0.5% glucose (CR). We have utilized 14C labelled nicotinic acid in the culture media combined with HPLC speciation and both UV and 14C detection to quantitate the total amounts of NAD+ and NADH and the amounts derived from the salvage pathway. We observed that wild-type and qpt1Delta yeast exclusively utilized extracellular nicotinic acid for NAD+ and NADH biosynthesis under both the 2% and 0.5% glucose growth conditions, suggesting that the de novo pathway plays little role if a functional salvage pathway is present. We also observed that NAD+ concentrations decreased in all three strains under CR. However, unlike the wild-type strain, NADH concentrations did not decrease and NAD+: NADH ratios did not increase under CR for either knockout strain. Lifespan analyses revealed that CR resulted in a lifespan increase of approximately 25% for the wild-type and qpt1Delta strains, while no increase in lifespan was observed for the npt1Delta strain. In combination, these data suggest that having a functional salvage pathway is required for lifespan extension under CR.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Carbon Radioisotopes / metabolism
  • Chromatography, High Pressure Liquid
  • Culture Media / chemistry
  • Gene Deletion
  • Genes, Fungal
  • Glucose / metabolism
  • Metabolic Networks and Pathways*
  • NAD / biosynthesis*
  • Niacin / metabolism
  • Pentosyltransferases / deficiency
  • Radiometry
  • Saccharomyces cerevisiae / metabolism*
  • Spectrum Analysis

Substances

  • Carbon Radioisotopes
  • Culture Media
  • NAD
  • Niacin
  • Pentosyltransferases
  • nicotinate-nucleotide diphosphorylase (carboxylating)
  • nicotinate phosphoribosyltransferase
  • Glucose