title: Secretion of quinolinic acid, an intermediate in the kynurenine pathway, for utilization in NAD+ biosynthesis in the yeast Saccharomyces cerevisiae.
abstract: NAD(+) is synthesized from tryptophan either via the kynurenine (de novo) pathway or via the salvage pathway by reutilizing intermediates such as nicotinic acid or nicotinamide ribose. Quinolinic acid is an intermediate in the kynurenine pathway. We have discovered that the budding yeast Saccharomyces cerevisiae secretes quinolinic acid into the medium and also utilizes extracellular quinolinic acid as a novel NAD(+) precursor. We provide evidence that extracellular quinolinic acid enters the cell via Tna1, a high-affinity nicotinic acid permease, and thereby helps to increase the intracellular concentration of NAD(+). Transcription of genes involved in the kynurenine pathway and Tna1 was increased, responding to a low intracellular NAD(+) concentration, in cells bearing mutations of these genes; this transcriptional induction was suppressed by supplementation with quinolinic acid or nicotinic acid. Our data thus shed new light on the significance of quinolinic acid, which had previously been recognized only as an intermediate in the kynurenine pathway.
authors: Laboratory of Basic and Applied Molecular Biotechnology, Division of Food and Biological Science, Graduate School of Agriculture, Kyoto University, Uji, Kyoto, Japan.
authors: Kazuto
authors: K
authors: Ohashi
authors: Shigeyuki
authors: S
authors: Kawai
authors: Kousaku
authors: K
authors: Murata
mesh_terms: D053898:Biosynthetic Pathways; D017077:Culture Media, Conditioned; D015870:Gene Expression; D055786:Gene Knockout Techniques; D005800:Genes, Fungal; D007737:Kynurenine / Q000096:biosynthesis*; D026901:Membrane Transport Proteins / Q000378:metabolism; D050296:Microbial Viability; D009243:NAD / Q000096:biosynthesis*; D010430:Pentosyltransferases / Q000235:genetics / Q000378:metabolism; D017378:Quinolinic Acid / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000502:physiology*; D014158:Transcription, Genetic
chemical_list: D017077:Culture Media, Conditioned; D026901:Membrane Transport Proteins; D009243:NAD; D007737:Kynurenine; D010430:Pentosyltransferases; C021864:nicotinate phosphoribosyltransferase; D017378:Quinolinic Acid