NBCe1 expression is required for normal renal ammonia metabolism
Mary E Handlogten1, Gunars Osis1, Hyun-Wook Lee1
1Division of Nephrology, Hypertension and Renal Transplantation, University of Florida College of Medicine, Gainesville, Florida;
American Journal of Physiology. Renal Physiology
|July 31, 2015
Summary
Proximal tubule Na(+)-coupled bicarbonate cotransporter (NBCe1) deletion reduces ammonia excretion. This study reveals NBCe1 is essential for normal renal ammonia metabolism and ammonia generation in the proximal tubule.
Area of Science:
- Nephrology
- Renal Physiology
- Molecular Biology
Background:
- Proximal tubule ammonia metabolism mechanisms are not fully understood.
- The basolateral electrogenic Na(+)-coupled bicarbonate cotransporter (NBCe1; Slc4a4) plays a role in renal acid-base balance.
- Its specific role in renal ammonia metabolism requires elucidation.
Purpose of the Study:
- To investigate the role of NBCe1 in regulating proximal tubule ammonia metabolism.
- To determine the impact of NBCe1 gene deletion on ammonia handling in the kidneys.
Main Methods:
- Utilized mice with heterozygous and homozygous NBCe1 gene deletion.
- Compared physiological parameters and protein expression in knockout and wild-type littermates.
- Analyzed serum bicarbonate, urinary pH, ammonia excretion, and key metabolic enzyme expression.
Main Results:
- NBCe1 deletion led to a gene dose-dependent decrease in serum bicarbonate.
- Urinary pH lowering capacity was maintained or enhanced.
- Despite metabolic acidosis, ammonia excretion decreased in a gene dose-dependent manner.
- Expression of key ammonia-generating enzymes (glutaminase, phosphoenolpyruvate carboxykinase) decreased, while ammonia-recycling enzyme (glutamine synthetase) increased.
- Expression of ammonia transporters (rhesus B/C glycoproteins) remained unchanged.
Conclusions:
- NBCe1 deletion significantly alters proximal tubule ammonia metabolism.
- NBCe1 is crucial for normal renal ammonia generation and excretion.
- The transporter is necessary for maintaining ammonia homeostasis within the proximal tubule.
More Related Videos
15:43Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes
Published on: January 7, 2013
18.7K
12:30Production of Nurr-1 Specific Polyclonal Antibodies Free of Cross-reactivity Against Its Close Homologs, Nor1 and Nur77
Published on: August 17, 2015
8.0K
Related Concept Videos
01:23Urea Cycle
52.1K
The urea cycle describes how liver cells convert ammonia to urea. Ammonia is a toxic waste product of protein catabolism. Land animals must convert ammonia into the less toxic urea which can be safely eliminated by the kidneys through urine. Marine animals excrete ammonia directly, and the surrounding water dilutes the ammonia to safe levels.
52.1K
01:22Inorganic Nitrogen Assimilation
823
Nitrogen is an essential element in biological systems, forming a crucial component of proteins, nucleic acids, and other cellular constituents. Many bacteria and archaea acquire nitrogen in the form of nitrate (NO₃⁻) or ammonia (NH₃), which are then assimilated into biomolecules through specific enzymatic pathways.Assimilatory Nitrate ReductionWhen nitrate enters the cell, it undergoes a two-step reduction process known as assimilatory nitrate reduction. Initially, the enzyme...
823
01:29Renal Regulation of Acid-Base Balance
2.4K
Metabolic reactions in the body produce nonvolatile acids, such as sulfuric acid, which generate an acid load of approximately 1 mEq of H+ per kilogram of body weight daily. Excreting H+ in the urine is essential to balance this acid load.
In the kidneys, cells within the proximal convoluted tubules (PCT) and the collecting ducts secrete hydrogen ions (H+) into the tubular fluid. Specifically, in the PCT, Na+/H+ antiporters secrete H+ while reabsorbing Na+.
However, the intercalated cells in...
In the kidneys, cells within the proximal convoluted tubules (PCT) and the collecting ducts secrete hydrogen ions (H+) into the tubular fluid. Specifically, in the PCT, Na+/H+ antiporters secrete H+ while reabsorbing Na+.
However, the intercalated cells in...
2.4K
01:20Overview of Nitrogen Metabolism
12.5K
Nitrogen is a very important element for life because it is a major constituent of proteins and nucleic acids. It is a macronutrient, and in nature, it is recycled from organic compounds and stored in the form of ammonia, ammonium ions, nitrate, nitrite, or nitrogen gas by many metabolic processes. Many of these metabolic processes are carried out only by prokaryotes.
The largest pool of nitrogen available in the terrestrial ecosystem is gaseous nitrogen (N2) from the air, but this...
The largest pool of nitrogen available in the terrestrial ecosystem is gaseous nitrogen (N2) from the air, but this...
12.5K
01:07Amines: Introduction
6.3K
Amines are organic derivatives of ammonia. They are formed by replacing one or more ammonia protons with alkyl or aryl groups. Depending upon the number of organyl groups bonded to nitrogen, amines are classified as primary, secondary, or tertiary. Primary amines have one organyl group attached to the nitrogen atom, while secondary and tertiary amines have two and three organyl groups attached to the nitrogen atom, respectively.
6.3K
01:10Nephrons
9.1K
The kidneys are intricate organs with millions of working units known as nephrons. Each nephron features two major structures: the renal corpuscle, which facilitates blood plasma filtration, and the renal tubule, which handles the glomerular filtrate. Blood supply is directly linked to the nephrons. The renal corpuscle consists of the glomerulus, a capillary network, and the Bowman's capsule, a double-walled epithelial structure that encases the glomerulus. The filtering of blood plasma...
9.1K