Studies on a unique organelle localization of a liver enzyme, serine:pyruvate (or alanine:glyoxylate) aminotransferase.

Serine:pyruvate (or alanine:glyoxylate) aminotransferase (SPT or AGT) in the liver is unique in that its subcellular distribution is entirely peroxisomal in man and herbivores, and largely mitochondrial in carnivores. In rats, this enzyme is located in both mitochondria and peroxisomes and only the mitochondrial activity is markedly induced by glucagon. The mechanism of the species-specific dual organelle localization is either transcription of the gene from two different start sites or loss of upstream translation initiation ATG codon by mutations. In herbivores, peroxisomal localization of SPT appears to be indispensable to prevent excessive oxalate production by removing glyoxylate, an immediate precursor of oxalate, formed from glycolate in this organelle. In carnivores, its mitochondrial localization appears to be needed to metabolize glyoxylate formed from L-hydroxyproline in mitochondria. In addition, SPT contributes substantially to gluconeogenesis from serine in rabbit, human and dog livers, irrespective of its mitochondrial or peroxisomal localization. (Communicated by Shigetada Nakanishi, M.J.A.).