Recombinant Human GRHPR Protein: Function & Research Use

Recombinant Human GRHPR Protein is a recombinant form of the human glyoxylate reductase/hydroxypyruvate reductase enzyme, essential for regulating glyoxylate and hydroxypyruvate levels in human metabolism and critically linked to the pathogenesis of primary hyperoxaluria type 2.

Protein Name

Glyoxylate Reductase/Hydroxypyruvate Reductase (GRHPR)

Species

Human (Homo sapiens)

Aladdin SKU

rp371345

Protein Function

Catalyzes NADPH-dependent reduction of glyoxylate to glycolate and hydroxypyruvate to D-glycerate

Disease Relevance

Loss-of-function mutations cause Primary Hyperoxaluria Type 2 (PH2)

Research Applications

Enzymatic activity assays, oxalate metabolism studies, drug target validation, structural biology

What Is GRHPR? Gene, Structure, and Biological Function

GRHPR (Glyoxylate Reductase/Hydroxypyruvate Reductase; Gene ID: 9380) is a cytosolic enzyme encoded by the GRHPR gene located on human chromosome 9p13.2. It belongs to the D-isomer-specific 2-hydroxyacid dehydrogenase family and functions as a homodimer under physiological conditions.

GRHPR catalyzes two principal NADPH-dependent reductive reactions: (1) the reduction of glyoxylate to glycolate, and (2) the reduction of hydroxypyruvate to D-glycerate. By consuming glyoxylate—an otherwise reactive and toxic metabolite—GRHPR prevents its oxidation to oxalate, the insoluble calcium salt of which accumulates pathologically in kidney and other tissues.

GRHPR is expressed predominantly in the liver and kidney, tissues with high metabolic flux through the glyoxylate pathway, making it a critical gatekeeper for preventing oxalate overproduction in humans.

GRHPR Mutations and Primary Hyperoxaluria Type 2

Loss-of-function mutations in the GRHPR gene cause Primary Hyperoxaluria Type 2 (PH2), a rare autosomal recessive disorder characterized by excessive endogenous oxalate production, recurrent nephrolithiasis (kidney stones), nephrocalcinosis, and in severe cases, progressive renal failure and systemic oxalosis.

In PH2 patients, the inability to reduce glyoxylate leads to its accumulation and subsequent oxidation to oxalate by lactate dehydrogenase (LDH). Additionally, D-glycerate excretion in urine (L-glyceric aciduria) is a characteristic biochemical marker used in clinical diagnosis of PH2.

Research using recombinant GRHPR protein has been fundamental in characterizing disease-associated variants, understanding structure-function relationships, and evaluating candidate small-molecule therapies and RNA interference strategies targeting upstream enzymes in the glyoxylate pathway.

Research Applications of Recombinant Human GRHPR Protein

Recombinant Human GRHPR Protein (Aladdin SKU: rp371345) supports a broad range of in vitro research applications:

• Enzymatic Activity Assays: Used as a positive control or active enzyme source in NADPH-dependent spectrophotometric assays measuring glyoxylate or hydroxypyruvate reduction kinetics.
• Drug Discovery and Target Validation: Enables high-throughput screening of small-molecule inhibitors or activators relevant to PH2 therapeutic development.
• Structural Biology: Suitable as a substrate for crystallography, cryo-EM, or hydrogen-deuterium exchange mass spectrometry studies of enzyme conformation and ligand binding.
• Biochemical Pathway Reconstitution: Used in cell-free systems to reconstitute the glyoxylate detoxification pathway for mechanistic studies.
• Antibody Validation: Acts as a positive control antigen for validating GRHPR-specific antibodies in Western blot, ELISA, and immunoprecipitation experiments.

Researchers are advised to verify specific activity, purity, and formulation details in the product datasheet prior to experimental design.

Handling, Storage, and Quality Considerations

To maintain the biological activity of Recombinant Human GRHPR Protein, researchers should observe the following best-practice guidelines:

• Storage: Store lyophilized or liquid formulations according to the manufacturer's datasheet instructions. Generally, recombinant proteins should be stored at −20 °C or −80 °C and avoid repeated freeze-thaw cycles.
• Reconstitution: Reconstitute lyophilized protein in the recommended buffer (typically sterile PBS with carrier protein such as BSA) to the suggested working concentration.
• Activity Verification: Confirm specific enzymatic activity prior to use in sensitive assays by performing a pilot NADPH consumption assay.
• Lot-to-Lot Consistency: For reproducibility, record the lot number for each experiment and request a Certificate of Analysis (CoA) confirming purity (typically assessed by SDS-PAGE) and biological activity.

Always consult the current product datasheet (available from Aladdin Scientific) for the most up-to-date storage conditions, formulation details, and quality specifications.

Frequently asked questions

What enzyme activities does recombinant human GRHPR protein possess?

Recombinant human GRHPR protein catalyzes two NADPH-dependent reductive reactions: the reduction of glyoxylate to glycolate, and the reduction of hydroxypyruvate to D-glycerate. These dual activities make it central to glyoxylate detoxification and oxalate homeostasis in human cells.

Why is GRHPR relevant to primary hyperoxaluria type 2 research?

Loss-of-function mutations in GRHPR impair glyoxylate reduction, leading to its accumulation and oxidation to oxalate, which causes PH2. Recombinant GRHPR protein is used in research to characterize pathogenic variants, understand enzyme structure-function relationships, and screen potential therapeutic compounds targeting this metabolic pathway.

How should recombinant human GRHPR protein be stored to maintain activity?

Recombinant human GRHPR protein should be stored according to the manufacturer's datasheet, typically at −20 °C or −80 °C. Repeated freeze-thaw cycles should be avoided to prevent loss of enzymatic activity. Always consult the Certificate of Analysis and product datasheet from Aladdin Scientific for lot-specific storage recommendations.

What expression system is used to produce recombinant human GRHPR protein?

The specific expression system for Aladdin's recombinant human GRHPR protein (SKU: rp371345) should be confirmed in the product datasheet or Certificate of Analysis. Common expression hosts for recombinant human proteins include E. coli, insect cells (baculovirus), and mammalian cell systems, each affecting glycosylation and folding properties.

References

1. Cramer SD, Ferree PM, Lin K, Milliner DS, Holmes RP. The gene encoding hydroxypyruvate reductase (GRHPR) is mutated in patients with primary hyperoxaluria type II. Hum Mol Genet. 1999;8(11):2063-2069. doi:10.1093/hmg/8.11.2063
2. Booth MP, Conners R, Rumsby G, Brady RL. Structural basis of substrate specificity in human glyoxylate reductase/hydroxypyruvate reductase. J Mol Biol. 2006;360(1):178-189. doi:10.1016/j.jmb.2006.04.066
3. Hoppe B. An update on primary hyperoxaluria. Nat Rev Nephrol. 2012;8(8):467-475. doi:10.1038/nrneph.2012.113

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