title: Nucleotide degradation and ribose salvage in yeast.
abstract: Nucleotide degradation is a universal metabolic capability. Here we combine metabolomics, genetics and biochemistry to characterize the yeast pathway. Nutrient starvation, via PKA, AMPK/SNF1, and TOR, triggers autophagic breakdown of ribosomes into nucleotides. A protein not previously associated with nucleotide degradation, Phm8, converts nucleotide monophosphates into nucleosides. Downstream steps, which involve the purine nucleoside phosphorylase, Pnp1, and pyrimidine nucleoside hydrolase, Urh1, funnel ribose into the nonoxidative pentose phosphate pathway. During carbon starvation, the ribose-derived carbon accumulates as sedoheptulose-7-phosphate, whose consumption by transaldolase is impaired due to depletion of transaldolase's other substrate, glyceraldehyde-3-phosphate. Oxidative stress increases glyceraldehyde-3-phosphate, resulting in rapid consumption of sedoheptulose-7-phosphate to make NADPH for antioxidant defense. Ablation of Phm8 or double deletion of Pnp1 and Urh1 prevent effective nucleotide salvage, resulting in metabolite depletion and impaired survival of starving yeast. Thus, ribose salvage provides means of surviving nutrient starvation and oxidative stress.
authors.affiliation: Lewis Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA.
authors.forename: Yi-Fan
authors.initials: YF
authors.lastname: Xu
authors.forename: Fabien
authors.initials: F
authors.lastname: Létisse
authors.forename: Farnaz
authors.initials: F
authors.lastname: Absalan
authors.forename: Wenyun
authors.initials: W
authors.lastname: Lu
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Kuznetsova
authors.forename: Greg
authors.initials: G
authors.lastname: Brown
authors.forename: Amy A
authors.initials: AA
authors.lastname: Caudy
authors.forename: Alexander F
authors.initials: AF
authors.lastname: Yakunin
authors.forename: James R
authors.initials: JR
authors.lastname: Broach
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Rabinowitz
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D005986:Glyceraldehyde 3-Phosphate / Q000378:metabolism; D009699:N-Glycosyl Hydrolases / Q000172:deficiency / Q000235:genetics*; D009249:NADP / Q000378:metabolism; D009711:Nucleotides / Q000378:metabolism*; D010427:Pentose Phosphate Pathway / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D011683:Purine-Nucleoside Phosphorylase / Q000172:deficiency / Q000235:genetics*; D012266:Ribose / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013312:Stress, Physiological / Q000235:genetics; D013403:Sugar Phosphates; D014153:Transaldolase / Q000235:genetics / Q000378:metabolism
chemical_list: D009711:Nucleotides; D029701:Saccharomyces cerevisiae Proteins; D013403:Sugar Phosphates; D005986:Glyceraldehyde 3-Phosphate; C020495:sedoheptulose 7-phosphate; D009249:NADP; D012266:Ribose; D014153:Transaldolase; D011683:Purine-Nucleoside Phosphorylase; C071570:SNF1-related protein kinases; D017346:Protein Serine-Threonine Kinases; C500749:target of rapamycin protein, S cerevisiae; D017868:Cyclic AMP-Dependent Protein Kinases; D055372:AMP-Activated Protein Kinases; D009699:N-Glycosyl Hydrolases; C454867:URH1 protein, S cerevisiae