Effect of dietary protein restriction on renal ammonia metabolism.
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.
Division of Nephrology, Hypertension and Transplantation, University of Florida College of Medicine, Gainesville, Florida.
Hyun-Wook
HW
Lee
Division of Nephrology, Hypertension and Transplantation, University of Florida College of Medicine, Gainesville, Florida.
Gunars
G
Osis
Division of Nephrology, Hypertension and Transplantation, University of Florida College of Medicine, Gainesville, Florida.
Mary E
ME
Handlogten
Division of Nephrology, Second Hospital of Shanxi Medical University, Yaiyuan, Shanxi, Peoples Republic of China; and.
Hui
H
Guo
Division of Nephrology, Hypertension and Transplantation, University of Florida College of Medicine, Gainesville, Florida.
Jill W
JW
Verlander
Division of Nephrology, Hypertension and Transplantation, University of Florida College of Medicine, Gainesville, Florida, Nephrology and Hypertension Section, Medical Service, North Florida/South Georgia Veterans Health System, Gainesville, Florida david.weiner@medicine.ufl.edu.
I David
http://orcid.org/0000-0002-0046-0600
ID
Weiner
D000641:Ammonia / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D018753:Diet, Protein-Restricted; D004044:Dietary Proteins / Q000378:metabolism*; D005974:Glutamate-Ammonia Ligase; D007685:Kidney Tubules, Collecting / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism; D008810:Mice, Inbred C57BL
D004044:Dietary Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D000641:Ammonia; D005974:Glutamate-Ammonia Ligase
acid base; ammonia; collecting duct; protein restriction; proximal tubule