Genetic defects in glyoxylate metabolism resulting in the three types of primary hyperoxaluria (PH)

In PH type I, the decreased or absent activity of the hepatic peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT), which normally converts glyoxylate to glycine, leads to an overproduction of oxalate and glycolate.

In PH type II, the decreased or absent activity of glyoxylate reductase/hydroxypyruvate reductase (GRHPR), which normally converts glyoxylate to glycolate, leads to an overproduction of oxalate and L-glycerate.

In PH type III, the activity of the mitochondrial 4-hydroxy-2-oxoglutarate aldolase (HOGA1), which normally catalyzes the cleavage of 4-hydroxy-2-oxoglutarate (HOG) to pyruvate and glyoxylate, is decreased or absent. Why this defect causes an increased oxalate production is unclear.