Abstract
Renal synthesis and excretion of ammonia are critical for efficient removal of acids from the body. Besides the rate of ammonia production, the intrarenal distribution of produced ammonia is a crucial step in the renal regulation of acid-base balance. Various acid-base disorders are associated not only with changes in ammonia production but also with its distribution between the urine and the renal veins. The final effect of ammonia production on acid-base balance largely depends on the events that determine the distribution of ammonia produced between urine and blood. Several factors, among which urine pH, urine flow, total ammonia production “per se” and renal blood flow may affect the percent of ammonia excreted into urines in humans with different acid-base disturbances. Among these factors, urine pH is the most important. An additional effect of stimulated ammoniagenesis is kidney hypertrophy. In tubule epithelial cells, the associated increase in ammonia production, rather than the acidosis per se, is responsible for favoring tubular hypertrophy. This effect is related to the inhibition of protein degradation, owing to changes in lysosomal pH and cathepsin activity, without effects on cell cycle. Both changes of PI-3 kinase pathway and the suppression of chaperone-mediated autophagy are candidate mechanism for ammonia-mediated inhibition of protein degradation in tubule cells. Available data in humans indicate that the response of kidney to metabolic acidosis includes both changes in amino acid uptake and suppression of protein degradation. The latter effect is associated woth the increase in ammonia excretion and partition into the urine.
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Acknowledgements
This study was supported by grants from the Ministero dell’Università e della Ricerca Scientifica e Tecnologica (PRIN), the University of Genoa, and the ISN/Baxter CEC Extramural Grant Program.
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Garibotto, G., Verzola, D., Sofia, A. et al. Mechanisms of renal ammonia production and protein turnover. Metab Brain Dis 24, 159–167 (2009). https://doi.org/10.1007/s11011-008-9121-6
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DOI: https://doi.org/10.1007/s11011-008-9121-6