title: Metabolic and mind shifts: from glucose to glutamine and acetate addictions in cancer.
abstract: OBJECTIVE
  Glutamine and acetate were recently identified as alternatives to glucose for fueling the tricarboxylic acid (TCA) cycle in cancer cells, particularly in the context of hypoxia.
  
  
  RESULTS
  Molecular mechanisms orchestrating glutamine and acetate metabolism were elicited through the combination of C tracer analysis and genetic silencing, or pharmacological modulation of key metabolic enzymes including those converting glutamate into α-ketoglutarate (αKG) (and beyond) and acetate into acetyl-coenzyme A (CoA).
  
  
  CONCLUSIONS
  Oxidative decarboxylation and reductive carboxylation of αKG represent two options for the glutamine metabolism. The canonical forward mode of the TCA cycle fuelled by glutamine may benefit from the decarboxylation of malate into pyruvate for fueling pyruvate dehydrogenase and generating acetyl-CoA to offer a self-sustainable TCA cycle. Under hypoxia and mutations in the TCA cycle, the reductive carboxylation of glutamine-derived αKG into citrate mainly supports lipogenesis via the ATP citrate lyase that cleaves citrate into oxaloacetate and acetyl-CoA. Still, a largely unsuspected source of acetyl-CoA was shown to derive from the direct ligation of acetate to CoA by acetyl-CoA synthetases. Altogether, these findings identify critical metabolic nodes in the glutamine and acetate metabolism as new determinants of tumor metabolic plasticity that may facilitate the design of synthetic lethal treatments.
authors.affiliation: Pole of Pharmacology and Therapeutics (FATH), Institut de Recherche Expérimentale et Clinique (IREC), Université catholique de Louvain, Brussels, Belgium.
authors.forename: Cyril
authors.initials: C
authors.lastname: Corbet
authors.forename: Olivier
authors.initials: O
authors.lastname: Feron
mesh_terms: D000085:Acetates / Q000378:metabolism*; D000105:Acetyl Coenzyme A / Q000378:metabolism; D045744:Cell Line, Tumor; D002951:Citrates / Q000378:metabolism; D002952:Citric Acid Cycle / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D006801:Humans; D000860:Hypoxia / Q000097:blood; D007656:Ketoglutaric Acids / Q000378:metabolism; D050155:Lipogenesis / Q000187:drug effects; D009369:Neoplasms / Q000378:metabolism*
chemical_list: D000085:Acetates; D002951:Citrates; D007656:Ketoglutaric Acids; D005973:Glutamine; D000105:Acetyl Coenzyme A; D005947:Glucose