Enzyme adaptation in mammals: the induction of glutaminase I in the guinea pig kidney
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An attempt was made to answer the question of whether the increase in renal glutaminase I (GIA) activity following chronic administration of ammonium chloride is the result of enzyme induction. The effect of chronic ammonium chloride administration on cellular GIA activity was studied in the kidney and liver. Renal GIA activity was also measured after chronic administration of adrenal steroids and protein. Finally, by the use of DL-ethionine, an attempt was made to show that the increased enzyme activity is due to the synthesis of new enzyme. Intragastric administration of 20 mEq. NH4Cl/kg. body weight/day to guinea pigs increased renal GIA activity sixty and eighty per cent above control values within two and four days respectively. Administration of 10 mEq. NH4Cl/kg. body weight/day raised renal GIA sixty per cent above control values, but there was no further rise after the second day. Intragastric administration of 20 mEq. sulfur/kg. body weight/day for four days increased renal glutaminase I activity eighty per cent above control values. In contrast to the above results, hepatic GIA did not increase in response to intragastric administration of 20 mEq. NH4Cl/kg. body weight/day or 20 mEq. sulfur/kg. body weight/day for four days. Neither desoxycorticosterone acetate (DOCA) nor hydrocortisone (40 mg./kg. body weight/day i.m. of each for two days) had any effect on renal GIA. Furthermore, DOCA administered simultaneously with NH4Cl did not produce a rise in renal GIA activity differing from NH4Cl administered alone. Casein hydrolysate (2.5 gm./day or 5 gm./day), orally, for two days increased renal GIA fifty per cent above control values. Thus, the rise in GIA appears to be specific for the kidney, uninfluenced by adrenal hormones but is affected by protein intake. The rise in renal GIA produced by intragastric administration of 20 mEq. NH4Cl/kg. body weight/day for two days can be completely inhibited by the simultaneous administration of DL-ethionine (2 mM/kg. body weight/day i.p.). Injection of this dose of DL-ethionine alone did not significantly effect basal renal GIA or ammonia excretion. Administration of DL-methionine along with DL-ethionine (2 mM/kg. body weight/day i.p. of each) and 20 mEq. NH4Cl/kg. body weight/day produced an increase in renal GIA that was no different than that produced by NH4Cl alone. These results suggest that increased renal GIA following chronic administration of NH4Cl is the result of increased enzyme synthesis. However, conclusive proof of increased enzyme synthesis will have to await the development of methods for the purification of renal glutaminase I.
Thesis (Ph.D.)--Boston University