ArticleBiochimica et biophysica acta2012
4-Hydroxy-2-oxoglutarate aldolase inactivity in primary hyperoxaluria type 3 and glyoxylate reductase inhibition.
Article in Biochimica et biophysica acta, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 70 citations in OpenAlex.
- Diet- and sex-related changes of gut microbiota composition and functional profiles after 4 months of weight loss intervention.European journal of nutrition · 2021Trial
- Gene overexpression reduces inhibitory metabolites to enhance CHO cell growth and IgG1 production.NPJ systems biology and applications · 2026Article
- Identification of Primary Hyperoxaluria Type III by Gas Chromatography/Mass Spectrometry-Based Urine Metabolomics.Metabolites · 2026Article
- Normal urinary oxalate excretion in 4-hydroxy-2-oxo-glutarate aldolase 1 (HOGA1) deficient mice with AGT expression in peroxisomes and not in mitochondria.Biochimica et biophysica acta. Molecular basis of disease · 2025Article
- Characterization of CHK-336, A First-in-Class, Liver-Targeted, Small-Molecule Lactate Dehydrogenase Inhibitor for Hyperoxaluria Treatment.Journal of the American Society of Nephrology : JASN · 2025Article
- Human glyoxylate metabolism revisited: New insights pointing to multi-organ involvement with implications for siRNA-based therapies in primary hyperoxaluria.Journal of inherited metabolic disease · 2025Review
- Metallomic Approach to Mercury and Selenium in the Liver Tissue ofInternational journal of molecular sciences · 2024Article
- Opportunities in Primary and Enteric Hyperoxaluria at the Cross-Roads Between the Clinic and Laboratory.Kidney international reports · 2024Article
- 4-hydroxy-2-oxoglutarate metabolism in a mouse model of Primary Hyperoxaluria Type 3.Biochemistry and biophysics reports · 2024Article
- Navigating the Evolving Landscape of Primary Hyperoxaluria: Traditional Management Defied by the Rise of Novel Molecular Drugs.Biomolecules · 2024Review
- HOGA1 variants in Chinese patients with primary hyperoxaluria type 3: genetic features and genotype-phenotype relationships.World journal of urology · 2023Article
- Natural and synthetic 2-oxoglutarate derivatives are substrates for oncogenic variants of human isocitrate dehydrogenase 1 and 2.The Journal of biological chemistry · 2023Article
- Genotype and Phenotype Characteristics of Chinese Pediatric Patients with Primary Hyperoxaluria.Human mutation · 2023Article
- Nedosiran, a Candidate siRNA Drug for the Treatment of Primary Hyperoxaluria: Design, Development, and Clinical Studies.ACS pharmacology & translational science · 2022Review
- Therapeutic RNA interference: A novel approach to the treatment of primary hyperoxaluria.British journal of clinical pharmacology · 2022Review
- Catabolism of Hydroxyproline in Vertebrates: Physiology, Evolution, Genetic Diseases and New siRNA Approach for Treatment.International journal of molecular sciences · 2022Review
- Integrative Functional Genomic Analysis in Multiplex Autism Families from Kazakhstan.Disease markers · 2022Article
- Novel therapeutic approaches for the primary hyperoxalurias.Pediatric nephrology (Berlin, Germany) · 2021Review
- Future treatments for hyperoxaluria.Current opinion in urology · 2020Review
- The effects of the inactivation of Hydroxyproline dehydrogenase on urinary oxalate and glycolate excretion in mouse models of primary hyperoxaluria.Biochimica et biophysica acta. Molecular basis of disease · 2020Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Mutations in the gene encoding for 4-hydroxy-2-oxoglutarate aldolase (HOGA) are associated with an excessive production of oxalate in Primary Hyperoxaluria type 3 (PH3). This enzyme is the final step of the hydroxyproline degradation pathway within the mitochondria and catalyzes the cleavage of 4-hydroxy-2-oxoglutarate (HOG) to pyruvate and glyoxylate. No analyses have been performed to assess the consequences of the mutations identified, particularly for those variants that produce either full-length or nearly full-length proteins. In this study, the expression, stability, and activity of nine PH3 human HOGA variants were examined. Using recombinant protein produced in Escherichia coli as well as transfected Chinese hamster ovary (CHO) cells, it was found that all nine PH3 variants are quite unstable, have a tendency to aggregate, and retain no measurable activity. A buildup of HOG was confirmed in the urine, sera and liver samples from PH3 patients. To determine how HOG is cleaved in the absence of HOGA activity, the ability of N-acetylneuraminate aldolase (NAL) to cleave HOG was evaluated. NAL showed minimal activity towards HOG. Whether the expected buildup of HOG in mitochondria could inhibit glyoxylate reductase (GR), the enzyme mutated in PH2, was also evaluated. GR was inhibited by HOG but not by 2-hydroxyglutarate or 2-oxoglutarate. Thus, one hypothetical component of the molecular basis for the excessive oxalate production in PH3 appears to be the inhibition of GR by HOG, resulting in a phenotype similar to PH2.
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