Jun 1, 1976

Effect of fatty acids on the disposition of ammonia

The Journal of Pharmacology and Experimental Therapeutics
R F Derr, L Zieve


Subcoma doses of fatty acids and ammonium salts injected intraperitoneally at the same time into rats or cats act synergistically to produce coma. Under these circumstances, the blood ammonia, is more than double that when the NH4+ is given alone. After these observations a rat liver homogenate system was utilized to study the effect of fatty acids on ammonia utilization in urea, glutamate and glutamine synthesis in vitro. Acetylglutamate-catalyzed urea synthesis was completely inhibited by 45 mM octanoate and was depressed 46% by 9.5 mM octanoate. Citrulline synthesis was similarly inhibited 86 and 28%, respectively. The concentration of liver octanoate at the moment of occurrence of coma after an in vivo injection was approximately 10 mM. The inhibitory effect of fatty acids on the utilization of NH4+ in the urea cycle was greater the longer the fatty acid chain. The critical step in this interference with ammonia metabolism was the inhibition of carbamyl phosphate synthetase. Argininosuccinate synthetase activity was also inhibited to a lesser degree, but ornithine transcarbamylase, argininosuccinate lyase and arginase were unaffected. Glutamate dehydrogenase was likewise inhibited in liver (83%) and brain (43%) by 13 mM oct...Continue Reading

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Mentioned in this Paper

Metabolic Process, Cellular
Ammonium salts
Coma (genus)
Argininosuccinate LYASE
Depressed - Symptom
Urea Cycle

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