Aminooxy acetic acid: a selective inhibitor of alanine:glyoxylate aminotransferase and its use in the diagnosis of primary hyperoxaluria type I.

The diagnosis of primary hyperoxaluria type I is usually based on the determination of the activity of the hepatic peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT). The activity observed, however, is due to the action of at least one more enzyme, i.e. glutamate:glyoxylate aminotransferase (GGT). Correction for the AGT activity displayed by GGT is usually made by use of a correction factor which correlates the activity of GGT with the amount of 'AGT' activity exhibited by GGT. This method, however, has a number of drawbacks: it corrects for only one other enzyme and it requires a second, rather insensitive and laborious enzyme assay to be performed which cannot be adapted to a centrifugal analyser. We therefore developed a simple and direct method for measurement of 'true' AGT activity which uses 100 mumol/l aminooxy acetic acid. Under these conditions AGT is completely inhibited and the contribution of GGT (and possibly other transaminases) to the L-alanine mediated transamination of glyoxylate can be measured directly. The 'true' AGT activities measured by this method correlated well with those measured in samples depleted of AGT by immunoprecipitation. Finally, this method proved to be fully compatible with the automated assay of AGT in a centrifugal analyser.