Endogenous synthesis of oxalate has been reported to increase in vitamin B6 deficiency probably due to defective transamination of glyoxylate, the direct source of oxalate, to glycine. Alanine:glyoxylate aminotransferase (AGT) in the liver catalyzes most of the glyoxylate transamination in mammalian tissues (E. V. Rowsell, K. Snell, J. A. Carnie, and K. V. Rowsell (1972)Biochem. J.127, 155-165). The effects of vitamin B6 deficiency on hepatic AGT isoenzymes, designated AGT 1 and AGT 2, respectively, were examined with male rats; AGT 1 is located both in the peroxisomes and in the mitochondria, and AGT 2 only in the mitochondria. The holo activity of combined peroxisomal and mitochondrial AGT 1 with a low Km for l-alanine rapidly decreased after a lag time of about 2 days during feeding of the vitamin B6-deficient diet (by 50% in 5 days, by 86% in 14 days). Peroxisomal AGT 1 activity was more affected than the mitochondrial. The holo activity of AGT 2 with a high Km for l-alanine decreased more slowly than AGT 1 (by 33% in 14 days, by 60% in 28 days). Urinary excretion of oxalate began to increase in 8-9 days, when AGT 2 remained intact but most of AGT 1 is depleted. When the defect in the glyoxylate transamination in vivo in vitamin B6 deficiency is considered, these findings suggest that it is due to the deficiency of AGT 1. The importance of peroxisomal AGT 1 is discussed, since peroxisomes have been described to be probably the major site of glyoxylate formation.
ASJC Scopus subject areas
- Molecular Biology