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A conserved phosphatase destroys toxic glycolytic side products in mammals and yeast

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Collard, François Baldin, Francesca [UCL] Gerin, Isabelle [UCL] Bolsée, Jennifer Noël, Gaëtane Veiga da Cunha, Maria [UCL] Vertommen, Didier [UCL] Houddane, Amina [UCL] Rider, Mark H. [UCL] Van Schaftingen, Emile [UCL] Bommer, Guido [UCL]

Metabolic enzymes are very specific. However, most of them show weak side activities toward compounds that are structurally related to their physiological substrates, thereby producing side products that may be toxic. In some cases, 'metabolite repair enzymes' eliminating side products have been identified. We show that mammalian glyceraldehyde 3-phosphate dehydrogenase and pyruvate kinase, two core glycolytic enzymes, produce 4-phosphoerythronate and 2-phospho-L-lactate, respectively. 4-Phosphoerythronate strongly inhibits an enzyme of the pentose phosphate pathway, whereas 2-phospho-L-lactate inhibits the enzyme producing the glycolytic activator fructose 2,6-bisphosphate. We discovered that a single, widely conserved enzyme, known as phosphoglycolate phosphatase (PGP) in mammals, dephosphorylates both 4-phosphoerythronate and 2-phospho-L-lactate, thereby preventing a block in the pentose phosphate pathway and glycolysis. Its yeast ortholog, Pho13, similarly dephosphorylates 4-phosphoerythronate and 2-phosphoglycolate, a side product of pyruvate kinase. Our work illustrates how metabolite repair enzymes can make up for the limited specificity of metabolic enzymes and permit high flux in central metabolic pathways.

Document type Article de périodique (Journal article) – Article de recherche
Publication date 2016
Language Anglais
Journal information "Nature Chemical Biology" - Vol. 12, no. 8, p. 601-607 (2016)
Peer reviewed yes
Publisher Nature Publishing Group ((United Kingdom) London)
issn 1552-4450
e-issn 1552-4469
Publication status Publié
Affiliations UCL - SSS/DDUV/BCHM - Biochimie-Recherche métabolique
UCL - SSS/DDUV/PHOS - Protein phosphorylation
Links
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Bibliographic reference Collard, François ; Baldin, Francesca ; Gerin, Isabelle ; Bolsée, Jennifer ; Noël, Gaëtane ; et. al. A conserved phosphatase destroys toxic glycolytic side products in mammals and yeast. In: Nature Chemical Biology, Vol. 12, no. 8, p. 601-607 (2016)
Permanent URL http://hdl.handle.net/2078.1/175323