Recent developments in our understanding of primary hyperoxaluria type 2

Hydroxypyruvate reductase (KPR) has been partially purified from human live r and can be separated into at least two forms by chromatofocusing; these f orms 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 NADP H as a cofactor. However, only peak B was able to reduce hydroxypyruvate an d glyoxylate, with a K-m, of 2.3 mM for the latter substrate. Peak A coelut ed with lactate dehydrogenase and could represent lactate dehydrogenase (wh ich is known to reduce hydroxypyruvate) alone or a mixture of proteins with HPR activity. The K-m, for hydroxypyruvate of the enzyme(s) in peak A (8 m M) was 80 times greater than that of peak B (0.1 mM), suggesting that the H PR enzyme contained in peak B may be more important physiologically, where the hydroxypyruvate concentrations are in the micromolar range. The data pr esented provide a biochemical explanation for the previously observed diffe rences in the tissue distribution of HPR and glyoxylate reductase activitie s in human subjects and support the claim that diagnoses of primary hyperox aluria type 2 should be made by measurement of glyoxylate reductase activit y in the liver.