Figure 1.

Biosynthesis of calcium oxalate. Glyoxylate is the main precursor of oxalate which combines spontaneously with calcium ions to form calcium oxalate. Names of enzymes: 1, serine hydroxymethyltransferase; 2, D-amino acid oxidase; 3, alanine:glyoxylate aminotransferase (AGT); 4, glyoxylate reductase-hydroxypyruvate reductase (GRHPR); 5, glycolate oxidase; 6, alcohol dehydrogenase; 7, aldehyde dehydrogenase; 8, lactate dehydrogenase; and 9, five enzyme-catalyzed reactions. PH1 results from mutations in AGT which is a hepatic peroxisomal enzyme. PH2 results from mutations in GRHPR which is a cytosolic enzyme found in several tissues, but primarily the liver. PH3 results from defects in the hepatic mitochondrial enzyme 4-hydroxy-2-oxoglutarate (HOG) aldolase which converts HOG and glyoxylate to pyruvate (reaction not shown), the last step in hydroxyproline catabolism. The reason why a deficiency of HOG aldolase activity increases oxalate production is obscure.