An Investigation into the Possible Contribution to Oxalogenesis of a Pathway Involving Thiazolidine-2, 4-Dicarboxylate

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In animals, oxalate is a harmful end product of metabolism and is produced primarily from glyoxylate in the liver. Herbivores including man are equipped with serine : pyruvate/alanine : glyoxylate aminotransferase (SPT/AGT) in liver peroxisomes to remove glyoxylate formed in this organelle and thus to prevent overproduction of oxalate. A question arises as to why oxalate should be formed in animals. In the present study, I aimed at elucidating the mechanism of oxalate production from glyoxylate in the liver. A possibility that glycolate oxidase catalyzes consecutive oxidations of glycolate to glyoxylate and further to oxalate has been proven unlikely. Possible contribution of a pathway involving thiazolidine carboxylates formed by condensation of glyoxylate with cysteine or cysteamine has been examined extensively, and was shown to be minor, if any, under the conditions used. The reported peroxisomal localization of lactate dehydrogenase (LDH) activity was most probably due to absorption of this enzyme to peroxisomal membrane. Since the activity of LDH in the liver is very high, however, it was considered to be likely that a portion of glyoxylate released from peroxisomes is oxidized by this cytosolic enzyme to oxalate, although the concentration of glyoxylate in liver cytosol is much lower than that of lactate. In order to investigate this possibility kinetically a simpler model system was looked for and found that a non-pathogenic and non-oxalate-producing mutant of a pathogenic bacteria of rice plant, pseudomonas glumae, produces oxalate when glyoxylate was supplied exogenously. Kinetic studies with the mutant Ps.glumae are under way.