Recent developments in our understanding of primary hyperoxaluria type 2.

Abstract

Hydroxypyruvate reductase (HPR) has been partially purified from human liver and can be separated into at least two forms by chromatofocusing; these forms therefore differ in their pI values. Both forms, one with a pI of >7.2 (peak A) and the other with a pI between pH 6.5 and 5.5 (peak B), use NADPH as a cofactor. However, only peak B was able to reduce hydroxypyruvate and glyoxylate, with a Km of 2.3 mM for the latter substrate. Peak A coeluted with lactate dehydrogenase and could represent lactate dehydrogenase (which is known to reduce hydroxypyruvate) alone or a mixture of proteins with HPR activity. The Km for hydroxypyruvate of the enzyme(s) in peak A (8 mM) was 80 times greater than that of peak B (0.1 mM), suggesting that the HPR enzyme contained in peak B may be more important physiologically, where the hydroxypyruvate concentrations are in the micromolar range. The data presented provide a biochemical explanation for the previously observed differences in the tissue distribution of HPR and glyoxylate reductase activities in human subjects and support the claim that diagnoses of primary hyperoxaluria type 2 should be made by measurement of glyoxylate reductase activity in the liver.