Effect of dietary protein restriction on renal ammonia metabolism.

Abstract

Dietary protein restriction has multiple benefits in kidney disease. Because protein intake is a major determinant of endogenous acid production, it is important that net acid excretion change in parallel during protein restriction. Ammonia is the primary component of net acid excretion, and inappropriate ammonia excretion can lead to negative nitrogen balance. Accordingly, we examined ammonia excretion in response to protein restriction and then we determined the molecular mechanism of the changes observed. Wild-type C57Bl/6 mice fed a 20% protein diet and then changed to 6% protein developed an 85% reduction in ammonia excretion within 2 days, which persisted during a 10-day study. The expression of multiple proteins involved in renal ammonia metabolism was altered, including the ammonia-generating enzymes phosphate-dependent glutaminase (PDG) and phosphoenolpyruvate carboxykinase (PEPCK) and the ammonia-metabolizing enzyme glutamine synthetase. Rhbg, an ammonia transporter, increased in expression in the inner stripe of outer medullary collecting duct intercalated cell (OMCDis-IC). However, collecting duct-specific Rhbg deletion did not alter the response to protein restriction. Rhcg deletion did not alter ammonia excretion in response to dietary protein restriction. These results indicate 1) dietary protein restriction decreases renal ammonia excretion through coordinated regulation of multiple components of ammonia metabolism; 2) increased Rhbg expression in the OMCDis-IC may indicate a biological role in addition to ammonia transport; and 3) Rhcg expression is not necessary to decrease ammonia excretion during dietary protein restriction.

• Authors: Hyun-Wook Lee, Gunars Osis, Mary E Handlogten, Hui Guo, Jill W Verlander, I David Weiner
• Journal: American journal of physiology. Renal physiology (Am J Physiol Renal Physiol) Vol. 308 Issue 12 Pg. F1463-73 (Jun 15 2015) ISSN: 1522-1466 [Electronic] United States
• PMID: 25925252 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Dietary Proteins
• Membrane Glycoproteins
• Membrane Transport Proteins
• Ammonia
• Glutamate-Ammonia Ligase

Topics

• Ammonia (metabolism)
• Animals
• Biological Transport (physiology)
• Diet, Protein-Restricted
• Dietary Proteins (metabolism)
• Glutamate-Ammonia Ligase
• Kidney Tubules, Collecting (metabolism)
• Membrane Glycoproteins (metabolism)
• Membrane Transport Proteins (metabolism)
• Mice, Inbred C57BL