3-Hydroxyglutaric Acid

• CAT Number: R007668
• CAS Number: 638-18-6
• Molecular Formula: C5H8O5
• Molecular Weight: 148.114
• Purity: ≥95%
• Synonyms: 3-Hydroxy-pentanedioic Acid; 2,4-Dideoxypentaric Acid; β-Hydroxyglutaric Acid
• Target: Endogenous Metabolite
• Storage: -20°C
• IUPAC Name: 3-hydroxypentanedioic acid
• InChI: InChI=1S/C5H8O5/c6-3(1-4(7)8)2-5(9)10/h3,6H,1-2H2,(H,7,8)(H,9,10)
• InChIKey: ZQHYXNSQOIDNTL-UHFFFAOYSA-N
• SMILES: C(C(CC(=O)O)O)C(=O)O

3-Hydroxyglutaric acid (CAS 638-18-6) is a glutaric acid derivative which is the byproduct of glutaric acidemia type I. Glutaric aciduria type I (glutaryl-CoA dehydrogenase deficiency) is an inborn error of metabolism that usually manifests in infancy by an acute encephalopathic crisis and often results in permanent motor handicap. Studies indicate that 3-hydroxyglutaric acid can be used as biomarker for GCDH (glutaryl-CoA dehydrogenase) deficiency. 

Reference

1.Goodman, Stephen I., et al. "Glutaryl‐CoA dehydrogenase mutations in glutaric acidemia (type I): review and report of thirty novel mutations." Human mutation 12.3 (1998): 141-144.
2.Christensen, E., et al. "Correlation of genotype and phenotype in glutaryl-CoA dehydrogenase deficiency." Journal of inherited metabolic disease 27.6 (2004): 861-868.
3.JIMD Rep. 2019 Mar 26;47(1):30-34. doi: 10.1002/jmd2.12026. eCollection 2019 May.

 

Formation of 3-hydroxyglutaric acid in glutaric aciduria type I: in vitro participation of medium chain acyl-CoA dehydrogenase.Peters V(1), Morath M(1), Mack M(2), Liesert M(3), Buckel W(3), Hoffmann GF(1), Vockley J(4), Ghisla S(5), Zschocke J(6).

 

3-Hydroxyglutaric acid (3-OH-GA) in urine has been identified as the most reliable diagnostic marker for glutaric aciduria type I (GA I). We showed that hydratation of glutaconyl-CoA to 3-hydroxyglutaryl-CoA, which is subsequently hydrolyzed to 3-OH-GA, is efficiently catalyzed by 3-methylglutaconyl-CoA hydratase (3-MGH). We have now investigated whether mitochondrial acyl-CoA-dehydrogenases can convert glutaryl-CoA to glutaconyl-CoA. Short-chain acyl-CoA dehydrogenase (SCAD), medium-chain acyl-CoA dehydrogenase (MCAD), and long-chain acyl-CoA dehydrogenase (LCAD) accepted glutaryl-CoA as a substrate. The highest k cat of glutaryl-CoA was found for MCAD (0.12 ± 0.01 second-1) and was about 26-fold and 52-fold higher than those of LCAD and SCAD, respectively. The turnover of MCAD for glutaryl-CoA was about 1.5% of that of its natural substrate octanoyl-CoA. Despite high K m (above 600 μM) and low turnover rate, the oxidation of glutaryl-CoA by MCAD in combination with 3-MGH could explain the urinary concentration of 3-OH-GA in GA I patients.

 

DOI: 10.1002/jmd2.12026

PMCID: PMC6498835

PMID: 31240164