Showing metabocard for 2-Hydroxyglutarate (MMDBc0000675)

Record Information
Version1.0
StatusDetected and Quantified
Creation Date2020-12-10 18:52:29 UTC
Update Date2022-08-31 06:10:51 UTC
MiMeDB IDMMDBc0000675
Metabolite Identification
Common Name2-Hydroxyglutarate
Description2-Hydroxyglutarate exists in 2 isomers: L-2-hydroxyglutarate acid and D-2-hydroxyglutarate. Both the D and the L stereoisomers of hydroxyglutaric acid (EC 1.1.99.2) are found in body fluids. In humans it is part of butanoate metabolic pathway and can be produced by phosphoglycerate dehydrogenase (PHGDH). More specifically, the enzyme PHGDH catalyzes the NADH-dependent reduction of ?-ketoglutarate (AKG) to D-2-hydroxyglutarate (D-2HG). 2-hydroxyglutarate is also the product of gain-of-function mutations in the cytosolic and mitochondrial isoforms of isocitrate dehydrogenase (IDH). Additionally, 2-hydroxyglutarate can be converted to ?-ketoglutaric acid through the action of 2-hydroxyglutarate dehydrogenase (HGDH). Humans have to variants of this enzyme: D-2-hydroxyglutarate dehydrogenase (D2HGDH) and L-2-hydroxyglutarate dehydrogenase (L2HGDH). A deficiency in either of these two enzymes can lead to a disease known as 2-hydroxyglutaric aciduria. L-2-hydroxyglutaric aciduria (caused by loss of L2HGDH) is chronic, with early symptoms such as hypotonia, tremors, and epilepsy declining into spongiform leukoencephalopathy, muscular choreodystonia, mental retardation, and psychomotor regression. D-2-hydroxyglutaric aciduria (caused by loss of D2HGDH or gain of function of IDH) is rare, with symptoms including cancer, macrocephaly, cardiomyopathy, mental retardation, hypotonia, and cortical blindness. 2-hydroxyglutarate was the first oncometabolite (or cancer-causing metabolite) to be formally named or identified. In cancer it is either produced by overexpression of phosphoglycerate dehydrogenase (PHGDH) or is produced in excess by gain-of-function mutations in the cytosolic and mitochondrial isoforms of isocitrate dehydrogenase (IDH). IDH is part of TCA cycle and is generated in high abundance when IDH is mutated. 2-hydroxyglutarate is sufficiently similar in structure to 2-oxogluratate (2OG) that it is able to inhibit a range of 2OG-dependent dioxygenases, including histone lysine demethylases (KDMs) and members of the ten-eleven translocation (TET) family of 5-methylcytosine (5mC) hydroxylases. This inhibitory effect leads to alterations in the hypoxia induced factor (HIF)-mediated hypoxic response and alterations in gene expression through global epigenetic remodeling. The net effect is that 2-hydroxyglutarate causes a cascading effect that leads genetic perturbations and malignant transformation. Furthermore, 2-hydroxyglutarate is found to be associated with glutaric aciduria II, which is also an inborn error of metabolism. 2-Hydroxyglutarate has also been found to be a metabolite in Aspergillus (PMID: 6057807 ).
Structure
MOLSDFPDBSMILESInChI

MOL for #<Metabolite:0x0000564abc0cf000>

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3D MOL for #<Metabolite:0x0000564abc0cf000>
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3D SDF for #<Metabolite:0x0000564abc0cf000>
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3D-SDF for #<Metabolite:0x0000564abc0cf000>
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PDB for #<Metabolite:0x0000564abc0cf000>
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3D PDB for #<Metabolite:0x0000564abc0cf000>
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SMILES for #<Metabolite:0x0000564abc0cf000>
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INCHI for #<Metabolite:0x0000564abc0cf000>
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SynonymsNot Available
Chemical FormulaC5H8O5
Average Molecular Weight148.114
Monoisotopic Molecular Weight148.037173366
IUPAC NameNot Available
Traditional NameNot Available
CAS Registry NumberNot Available
SMILESNot Available
InChI Identifier
InChI=1S/C5H8O5/c6-3(5(9)10)1-2-4(7)8/h3,6H,1-2H2,(H,7,8)(H,9,10)
InChI KeyHWXBTNAVRSUOJR-UHFFFAOYSA-N