Glutaminase II Pathway in Human Kidney

Abstract

THE principal mechanism whereby excess hydrogen ions are excreted in man is by renal production of ammonia and subsequent urinary excretion as ammonium. The major and direct source of this renal ammoniagenesis is glutamine¹. Two distinct metabolic pathways of glutamine metabolism have been demonstrated in rat, guinea-pig and dog. The intramitochondrial glutaminase I isoenzymes which hydrolyse glutamine to ammonia and glutamic acid and its subsequent deamidation to ammonia and 2-oxo-glutarate constitute the major metabolic route in the rat². The extramitochondrial glutamine-aminotransferase-ω-amidase pathway (glutaminase II), however, has been shown to be important in the dog³. In man, whereas the glutaminase I pathway has been demonstrated⁴ there is no direct evidence for the latter metabolic pathway. We investigated this metabolic pathway using the alkyl substituted glutamine, L-γ-glutamylmethylamide. In contrast to glutamine, this substituted compound on deamidation yields methylamine⁵.