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Mitochondrion. 2014 Nov;19 Pt B:275-81. doi: 10.1016/j.mito.2014.02.009. Epub 2014 Feb 21.

Mitochondrial 2-hydroxyglutarate metabolism.

Author information

1
Division of Chemistry and Chemical Engineering, California Institute of Technology, Mail Code 210-41, Pasadena, CA 91125, United States.
2
Institute for Computer Science, Heinrich-Heine-University, Universitätsstr. 1, D-40225 Düsseldorf, Germany.
3
Institut of Developmental and Molecular Biology of Plants, Plant Molecular Physiology and Biotechnology Group, Heinrich-Heine-University, Universitätsstraße 1, 40225 Düsseldorf, Germany.
4
Institute for Computer Science, Heinrich-Heine-University, Universitätsstr. 1, D-40225 Düsseldorf, Germany; Cluster of Excellence on Plant Sciences (CEPLAS), 40225 Düsseldorf, Germany.
5
Institut of Developmental and Molecular Biology of Plants, Plant Molecular Physiology and Biotechnology Group, Heinrich-Heine-University, Universitätsstraße 1, 40225 Düsseldorf, Germany; Cluster of Excellence on Plant Sciences (CEPLAS), 40225 Düsseldorf, Germany. Electronic address: veronica.maurino@uni-duesseldorf.de.

Abstract

2-Hydroxyglutarate (2-HG) is a five-carbon dicarboxylic acid with a hydroxyl group at the alpha position, which forms a stereocenter in this molecule. Although the existence of mitochondrial D- and L-2HG metabolisms has long been known in different eukaryotes, the biosynthetic pathways, especially in plants, have not been completely elucidated. While D-2HG is involved in intermediary metabolism, L-2HG may not have a cellular function but it needs to be recycled through a metabolic repair reaction. Independent of their metabolic origin, D- and L-2HG are oxidized in plant mitochondria to 2-ketoglutarate through the action of two stereospecific enzymes, D- and L-2-hydroxyacid dehydrogenases. While plants are to a large extent unaffected by high cellular concentrations of D-2HG, deficiencies in the metabolism of D- and L-2HG result in fatal disorders in humans. We present current data gathered on plant D- and L-2HG metabolisms and relate it to existing knowledge on 2HG metabolism in other organisms. We focus on the metabolic origin of these compounds, the mitochondrial catabolic steps catalyzed by the stereospecific dehydrogenases, and phylogenetic relationships between different studied 2-hydroxyacid dehydrogenases.

KEYWORDS:

2-Hydroxyglutarate; Lysine metabolism; Metabolite repair; d-2-Hydroxyacid dehydrogenase; l-2-Hydroxyacid dehydrogenase

PMID:
24561575
DOI:
10.1016/j.mito.2014.02.009
[Indexed for MEDLINE]

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