CYTOSOLIC COMPARTMENTALIZATION OF HEPATIC ALANINE-GLYOXYLATE AMINOTRANSFERASE IN PATIENTS WITH ABERRANT PEROXISOMAL BIOGENESIS AND ITS EFFECT ON OXALATE METABOLISM

Two patients with atypical manifestations of aberrant peroxisomal biog enesis are described. Contrary to previous studies, which had shown th at Zellweger syndrome patients usually have normal levels of urinary o xalate excretion, the patients in the present study had evidence of ab normal oxalate metabolism in the form of hyperoxaluria and, in one of the patients, calcium oxalate urolithiasis. Activity of the liver-spec ific peroxisomal enzyme alanine: glyoxylate aminotransferase (AGT), wh ich is a major determinant of the level of endogenous oxalate synthesi s in humans, was normal in one patient and markedly supranormal in the other. Using the technique of post-embedding protein A-colloidal gold immunoelectron microscopy, AGT was found to be mainly cytosolic in th e livers of both patients, with significant amounts also localized in the nuclei. In a small minority of the hepatocytes of one patient, who was homozygous for the more common (major) AGT allele, large numbers of unidentified fibrillar arrays were found in the cytosol, which labe lled heavily for immunoreactive AGT. The background cytosolic AGT labe lling was markedly reduced in such cells when compared to the majority of cells that did not contain fibrils. In the other patient, who was heterozygous for the major and minor AGT alleles, there appeared to be low levels of mitochondrial AGT labelling. In the light of these data , the possible metabolic function of cytosolic AGT in the livers of pa nperoxisomal disease patients is discussed.