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Logo of jbcThe Journal of Biological Chemistry
J Biol Chem. 2016 March 18; 291(12): 6059.
PMCID: PMC4813584

Yeast Makes 2-Hydroxyglutarate as Part of Its Metabolism

Saccharomyces cerevisiae Forms d-2-Hydroxyglutarate and Couples Its Degradation to d-Lactate Formation via a Cytosolic Transhydrogenase

♦ See referenced article, J. Biol. Chem. 2016, 291, 6036–6058

In some inherited metabolic diseases and cancers, a stereoisomeric molecule called 2-hydroxyglutarate (2HG) is detectable. However, in yeast, not much is known about the presence and metabolism of 2HG. In this Paper of the Week, a team led by Carole L. Linster at the University of Luxembourg showed that yeastmake the d form of 2HG. The investigators found two homologs of human d-2HG dehydrogenase, Dld2 and Dld3, in yeast. Similar to its human counterpart, Dld2 is a mitochondrial protein. However, the cytosolic protein Dld3 degrades d-2HG. The enzyme is a FAD-dependent transhydrogenase that uses pyruvate as a hydrogen acceptor to convert d-2HG to α-ketoglutarate. The authors say, “Based on our observations, we propose that d-2HG is mainly formed and degraded in the cytosol of S. cerevisiae cells in a process that couples d-2HG metabolism to the shuttling of reducing equivalents from cytosolic NADH to the mitochondrial respiratory chain via the d-lactate dehydrogenase Dld1.”

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d-2HG formation and degradation in yeast.

Articles from The Journal of Biological Chemistry are provided here courtesy of American Society for Biochemistry and Molecular Biology