The purine nucleotide cycle. A pathway for ammonia production in the rat kidney.

Abstract

A B S T R A C T Particle-free extracts prepared from kidney cortex of rat catalyze the formation of ammonia via the purine nucleotide cycle. Compared with controls, extracts prepared from kidneys of rats fed ammonium chloride for 2 days show a 60% increase in adenylosuccinate synthetase and a threefold increase in adenylosuccinase activity, and a greater and more rapid synthesis of ammonia and adenine nucleotide from aspartate and inosine monophosphate. Extracts prepared from kidneys of rats fed a potassiumdeficient diet show a twofold increase in adenylosuccinate synthetase and a threefold increase in adenylosuccinase activity. In such extracts the rate of synthesis of ammonia and adenine nucleotide from aspartate and inosine monophosphate is also increased.These results show that the reactions of the purine nucleotide cycle are present and can operate in extracts of kidney cortex. The operational capacity of the cycle is accelerated by ammonium chloride feeding and potassium depletion, conditions known to increase renal ammonia excretion.Extracts of kidney cortex convert inosine monophosphate to uric acid. This is prevented by addition of allopurinol or 1-pyrophosphoryl ribose 5-phosphate to the reaction mix,ture.

Evidence that the Severity of Depletion of Inorganic Phosphate Determines the Severity of the Disturbance of Adenine Nucleotide Metabolism in the Liver and Renal Cortex of the Fructose-Loaded Rat

“…In the renal cortex, as in the liver, the deamination of AMP to inosine 5'-monophosphate can be brisk (51). In the isolated liver perfused with fructose, 10 mM, increasing the concentration of Pi in the perfusion medium from 1 to 10 mM prevented an otherwise sevenfold increase in concentration of inosine 5'-monophosphate (19).…”

Adenylosuccinate Syntheatase: Recent Developments

“…This reaction cycle is active in mammalian muscle (Lowenstein, 1972), brain (Schultz and Lowenstein, 1976), and kidney (Bogusky et al, 1976). This review covers structure and function, regulation (at the transcription and enzyme levels), and the metabolic roles of AMPSase, with emphasis on the literature published since the last review (Stayton et al, 1983).…”

In vitro Correlation of Glutamine and Glutamate Renal Ammoniagenesis during Adaptation

“…1-3). Also the extent that the purine nucleotide pathway can adapt ammoniagencsis seems limited [17], The burden of proof lies with those who feel the mechanisms behind the stimulatory changes in glutamate and glutamine ammoniagenesis differ. The most likely common site for adaptation would be at glutamate dehydrogenase [4], The data in the figures and the table also suggest that similar mechanisms are respon sible for renal ammonia adaptation during acuteandchronicacidosisin rats.…”