title: 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.
authors.affiliation: Department of Molecular Pathology, Windeyer Institute of Medical Sciences, University College London, United Kingdom.
authors.forename: D P
authors.initials: DP
authors.lastname: Cregeen
authors.forename: G
authors.initials: G
authors.lastname: Rumsby
mesh_terms: D000429:Alcohol Oxidoreductases / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D050537:Hydroxypyruvate Reductase; D006960:Hyperoxaluria, Primary / Q000209:etiology*; D008099:Liver / Q000201:enzymology; D009249:NADP / Q000378:metabolism
chemical_list: D009249:NADP; D000429:Alcohol Oxidoreductases; C020830:glyoxylate reductase; D050537:Hydroxypyruvate Reductase