Renal glutamine utilization: glycylglycine stimulation of γ-glutamyltransferase

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Abstract
Glycylglycine stimulation of renal glutamine utilization was studied on the homogenate, subcellular and purified enzyme level. The results establish the existence of 2 glutamine utilizing pathways, the mitochondrial dependent L-glutamine amidohydrolase (PDG) and a 2nd, extramitochondrial pathway. In contrast to the mitochondrial pathway which produces stoichiometric amounts of ammonia and glutamate, this second pathway hydrolyzes glutamine to produce ammonia and transfers the .gamma.-glutamyl moiety, producing .gamma.-glutamyl peptides. In the crude systems, containing cyclotransferase, the .gamma.-glutamyl moiety appears mainly as 5-oxoproline; in the enzyme preparation, purified 112-fold, .gamma.-glutamyl peptides (transpeptidation) and a small amount of glutamate (hydrolysis) appear. D-Glutamine was hydrolyzed, in contrast to the stereospecific PDG, but at < 1/2 the rate of the L-isomer. The MW of this extramitochondrial D- and L-glutamine utilizing enzyme was estimated by gel filtration on a Sephadex G-200 column and found to be .apprxeq. 70,000. Based on product formation, MW estimation and copurification with the activity responsible for p-nitroanilide release from .gamma.-glutamyl-p-nitroanilide, it is concluded that this reaction is catalyzed by .gamma.-glutamyltranspeptidase. Glycylglycine stimulated this enzyme to produce more ammonia while decreasing the appearance of glutamate; the mitochondrial glutaminase was unaffected by glycylglycine. This extramitochondrial glutamine utilizing pathway can make a significant contribution to in vivo renal ammoniagenesis.

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