The effect of vitamin B6 deficiency on alanine: Glyoxylate aminotransferase isoenzymes in rat liver

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 K_m 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 K_m 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.