Reference : A conserved phosphatase destroys toxic glycolytic side products in mammals and yeast |
Scientific journals : Article | |||
Life sciences : Biochemistry, biophysics & molecular biology Human health sciences : Endocrinology, metabolism & nutrition | |||
Systems Biomedicine | |||
http://hdl.handle.net/10993/38263 | |||
A conserved phosphatase destroys toxic glycolytic side products in mammals and yeast | |
English | |
Collard, François [] | |
Baldin, Francesca [] | |
Gerin, Isabelle [] | |
Bolsée, Jennifer [] | |
Noël, Gaëtane [] | |
Graff, Julie [] | |
Veiga-da-Cunha, Maria [] | |
Stroobant, Vincent [] | |
Vertommen, Didier [] | |
Houddane, Amina [] | |
Rider, Mark H [] | |
Linster, Carole ![]() | |
Van Schaftingen, Emile [] | |
Bommer, Guido T [] | |
Aug-2016 | |
Nature Chemical Biology | |
Nature Publishing Group | |
12 | |
8 | |
601-607 | |
Yes (verified by ORBilu) | |
International | |
1552-4450 | |
1552-4469 | |
New York | |
United Kingdom | |
[en] carbohydrates ; Enzyme mechanisms ; Metabolic pathways ; Metabolomics | |
[en] 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. | |
Luxembourg Centre for Systems Biomedicine (LCSB) ; de Duve Institute, Brussels ; Welbio, Belgium | |
Researchers ; Students | |
http://hdl.handle.net/10993/38263 | |
10.1038/nchembio.2104 |
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