Glyoxylate and hydroxypyruvate reductase (GRHPR)

Glyoxylate and hydroxypyruvate reductase (GRHPR) is a cytosolic enzyme that catalyzes two key redox reactions: reduction of glyoxylate to glycolate, thereby preventing glyoxylate accumulation, and reduction of hydroxypyruvate to D-glycerate, an intermediate in gluconeogenesis[1][2][5]. It uses both NADPH and NADH as cofactors[3]. Mutations in the GRHPR gene cause primary hyperoxaluria type 2, an autosomal recessive disorder characterized by excessive oxalate production leading to recurrent kidney stones, progressive kidney damage, and systemic deposition of calcium oxalate in body tissues[1][4][6]. GRHPR is classified as an oxidoreductase enzyme, and its deficiency represents a critical metabolic bottleneck in cellular glyoxylate and hydroxypyruvate metabolism. There are no currently approved drugs that directly modulate GRHPR activity; instead, current primary hyperoxaluria type 2 treatments are supportive and symptomatic[6].

Other names

Glyoxylate reductase/hydroxypyruvate reductaseGLXRD-glycerate dehydrogenasePrimary hyperoxaluria type 2 proteinGLYDMSTP035PH2 proteinEpididymis secretory sperm binding proteinGlycerate-2-dehydrogenase

No targeted pharmacological mechanism established. Therapies for primary hyperoxaluria type 2 are supportive or aimed at reducing substrate load (hydration, citrate supplementation)