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

1976 ◽  
Vol 58 (2) ◽  
pp. 326-335 ◽  
Author(s):  
R T Bogusky ◽  
L M Lowenstein ◽  
J M Lowenstein
1992 ◽  
Vol 70 (1) ◽  
pp. 132-141 ◽  
Author(s):  
T. E. Graham ◽  
D. A. MacLean

This review focuses on the ammonia and amino acid metabolic responses of active human skeletal muscle, with a particular emphasis on steady-state exercise. Ammonia production in skeletal muscle involves the purine nucleotide cycle and the amino acids glutamate, glutamine, and alanine and probably also includes the branched chain amino acids as well as aspartate. Ammonia production is greatest during prolonged, steady state exercise that requires 60–80% [Formula: see text] and is associated with glutamine and alanine metabolism. Under these circumstances it is unresolved whether the purine nucleotide cycle (AMP deamination) is active; if so, it must be cycling with no IMP accumulation. It is proposed that under these circumstances the ammonia is produced from slow twitch fibers by the deamination of the branched chain amino acids. The ammonia response can be suppressed by increasing the carbohydrate availability and this may be mediated by altering the availability of the branched chain amino acids. The fate of the ammonia released into the circulation is unresolved, but there is indirect evidence that a considerable portion may be excreted by the lung in expired air.Key words: glutamine, branched chain amino acids, glutamate dehydrogenase, purine nucleotide cycle.


1981 ◽  
Vol 196 (1) ◽  
pp. 323-326 ◽  
Author(s):  
R T Bogusky ◽  
K A Steele ◽  
L M Lowenstein

The effect of chronic acid feeding and its subsequent withdrawal was determined on the amounts of the metabolic intermediates and enzymic activities of the purine nucleotide cycle. Sprague-Dawley rats were given 1.5% (w/v) NH4Cl in their drinking water for 5 days. The renal excretion of NH3 rose 70-fold and the rats developed acidosis. The amount of renal IMP rose from a control value of 4.5 +/- 2.2 to 20.4 +/- 3.7nmol/g of kidney after 48h of acid feeding (P less than 0.001) and fell to normal within 48h of the recovery. Adenylosuccinate concentrations fell from a control value of 4.5 +/- 0.9nmol/g of kidney to 1.2 +/- 0.3nmol/g (P less than 0.005) by day 5 of acidosis and continued to fall to undetectable values by 48h after recovery. The amount of AMP remained constant through the acid-feeding and the recovery periods. The activity of adenylosuccinate synthetase, the rate-limiting enzyme of the purine nucleotide cycle, paralleled the rise and fall in NH3 excretion. The activities of phosphate-dependent glutaminase and glutamate dehydrogenase were elevated during the acid-feeding and the recovery period. Thus changes in the purine nucleotide cycle correlate with changes in NH3 excretion to a more parallel degree than does the activity of glutaminase or glutamate dehydrogenase.


Science ◽  
1971 ◽  
Vol 171 (3969) ◽  
pp. 397-400 ◽  
Author(s):  
J. Lowenstein ◽  
K. Tornheim

1988 ◽  
Vol 255 (6) ◽  
pp. F1122-F1127
Author(s):  
K. Tamura ◽  
H. Endou

To evaluate the contribution of the purine nucleotide cycle (PNC) in renal ammoniagenesis, ammonia production (AP) in cortical tubular suspensions and microdissected nephron segments of control and acidotic rats was determined using various amino acids, including glutamine (Gln) and aspartate (Asp). In the cortical tubular suspensions, the best substrate for ammoniagenesis was Gln (153.1 +/- 19.4 nmol.mg protein-1.15 min-1) followed by Asp (70.9 +/- 11.4). Metabolic acidosis resulted in a significant increase of AP only from Gln (316.5 +/- 36.1 nmol.mg protein-1.15 min-1, P less than 0.01 vs. control). Intranephron distribution of AP (pmol/mm or a glomerulus/15 min) from Gln showed that the first segment of the proximal tubule (S1) was highest in control (95.7 +/- 9.0), and its AP markedly increased in acidosis (221.6 +/- 8.3, P less than 0.001 vs. control). The most interesting and striking finding was that with Asp as a substrate, AP was maximal in S1 (165.0 +/- 32.8), with a value exceeding that from Gln. An adenylosuccinase inhibitor, 6-mercaptopurine (0.1 mM), significantly inhibited AP from Asp in S1 and S3, and from Gln in S1. On the contrary, a specific inhibitor of phosphoenolpyruvate carboxykinase, 3-mercaptopicolinate (0.1 mM), caused a significant decrease of AP from Gln, but not from Asp, in S1. From these results it could be concluded that AP via PNC can occur at high rates, especially in S1, only when Asp is present at high concentrations.


1983 ◽  
Vol 212 (3) ◽  
pp. 705-711 ◽  
Author(s):  
T Strzelecki ◽  
J Rogulski ◽  
S Angielski

To test the significance of the purine nucleotide cycle in renal ammoniagenesis, studies were conducted with rat kidney cortical slices using glutamate or glutamine labelled in the alpha-amino group with 15N. Glucose production by normal kidney slices with 2 mM-glutamine was equal to that with 3 mM-glutamate. With L-[15N]glutamate as sole substrate, one-third of the total ammonia produced by kidney slices was labelled, indicating significant deamination of glutamate or other amino acids from the cellular pool. Ammonia produced from the amino group of L-[alpha-15N]glutamine was 4-fold higher than from glutamate at similar glucose production rates. Glucose and ammonia formation from glutamine by kidney slices obtained from rats with chronic metabolic acidosis was found to be 70% higher than by normal kidney slices. The contribution of the amino group of glutamine to total ammonia production was similar in both types of kidneys. No 15N was found in the amino group of adenine nucleotides after incubation of kidney slices from normal or chronically acidotic rats with labelled glutamine. Addition of Pi, a strong inhibitor of AMP deaminase, had no effect on ammonia formation from glutamine. Likewise, fructose, which may induce a decrease in endogenous Pi, had no effect on ammonia formation. The data obtained suggest that the contribution of the purine nucleotide cycle to ammonia formation from glutamine in rat renal tissue is insignificant.


1986 ◽  
Vol 261 (22) ◽  
pp. 10157-10162
Author(s):  
K Tornheim ◽  
H Pang ◽  
C E Costello

1972 ◽  
Vol 247 (1) ◽  
pp. 162-169 ◽  
Author(s):  
Keith Tornheim ◽  
John M. Lowenstein

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