Enzymatic hydrolysis of glutamine and glutathione by glutaminase

(1) Data identify the enzyme responsible for the first step in the hydrolysis of glutathione, the cleavage of the gamma glutamyl bond, as the same enzyme responsible for the hydrolysis of glutamine to glutamic acid and ammonia is reported here. (2) Activation studies have suggested the role glutathione perhaps plays in the glutamine-glutaminase system. The Activation of glutaminase by trace amounts of ammonium ions in the hydrolysis of glutathione suggest that the body utilized the first step in the hydrolysis of this tripeptide to assure a constant supply of glutamine to the enzyme glutamines for the formation of urinary ammonia. (3) Inhibition studies have been described which make possible the assumption that another role of glutathione in the body is that a transport mechanism by which certain materials are carried to the kidney for excretion. (4) Studies of the physical properties of glutaminase have suggested that the glutaminase molecule represents a cation exchange resin within the tubules of the kidney. The ion studies described here have shown that glutaminase is influenced by the ionized material of the glomerular filtrate in two ways: at concentrations in which these ions are normally present in the blood, they activate the enzyme, but in higher concentrations these ions are inhibitory. These observations have been extended to form the basis of a theory explaing the mechanism by which the processes of reabsorption and secreation are carried out by the tubules of the kidney nephron.