Target type: biologicalprocess
The directed movement of ammonium ions from one side of an epithelium to the other. [GOC:mah, GOC:yaf]
Transepithelial ammonium transport is a critical process that involves the movement of ammonium (NH4+) across epithelial cell layers. This process is essential for maintaining acid-base homeostasis, regulating blood ammonia levels, and preventing the toxic accumulation of ammonia in the body. Here's a detailed breakdown of the biological process:
**1. Absorption in the Gut:**
* Dietary proteins are broken down into amino acids during digestion.
* Deamination of amino acids in the gut produces ammonia.
* Ammonium ions (NH4+) are generated from ammonia by the enzyme glutamine synthetase.
* These ammonium ions are absorbed across the intestinal epithelium into the bloodstream.
**2. Transport in the Blood:**
* Ammonium ions are transported in the bloodstream primarily as glutamine.
* Glutamine is synthesized from glutamate and ammonia in the liver and other tissues.
* It serves as a non-toxic carrier for ammonia in the blood.
**3. Excretion by the Kidney:**
* The kidneys play a crucial role in eliminating excess ammonium from the body.
* Ammonium ions are filtered from the blood in the glomerulus.
* In the proximal tubule, NH4+ is reabsorbed back into the blood.
* However, in the distal tubule and collecting duct, NH4+ is secreted into the tubular fluid.
* This secretion process is driven by a proton gradient generated by the action of the sodium-hydrogen exchanger (NHE3).
* The ammonium ions in the tubular fluid contribute to the formation of acidic urine, thus aiding in acid-base regulation.
**4. Secretion by the Liver:**
* The liver is another critical organ involved in ammonium removal.
* The liver converts ammonia to urea through the urea cycle.
* Urea is a less toxic form of ammonia that can be excreted in urine.
* The liver also contributes to ammonium excretion by secreting it into the bile.
**5. Transcellular and Paracellular Transport:**
* The movement of ammonium across epithelial cell layers involves both transcellular and paracellular pathways.
* Transcellular transport involves the movement of NH4+ through the epithelial cell membrane via specific transporters.
* These transporters include:
* **Rhesus glycoprotein (RhBG):** A bidirectional transporter that facilitates ammonium movement across the apical membrane.
* **Organic cation transporters (OCTs):** Transporters that can transport ammonium across the basolateral membrane.
* Paracellular transport refers to the passive diffusion of ammonium ions between epithelial cells through tight junctions.
**6. Regulation of Ammonium Transport:**
* Ammonium transport is tightly regulated to maintain ammonia homeostasis.
* Factors that influence ammonium transport include:
* **Dietary protein intake:** High protein intake leads to increased ammonia production and excretion.
* **Acid-base balance:** In acidosis, ammonium secretion increases to help buffer the excess acid.
* **Hormonal regulation:** Hormones like aldosterone and insulin can influence ammonium transport.
**7. Pathological Conditions:**
* Dysregulation of ammonium transport can lead to several pathological conditions.
* **Hyperammonemia:** Elevated blood ammonia levels can cause neurological damage and encephalopathy.
* **Hepatic encephalopathy:** Impaired liver function can result in ammonia accumulation and neurological dysfunction.
* **Kidney failure:** Reduced renal ammonium excretion contributes to hyperammonemia.
In summary, transepithelial ammonium transport is a complex and tightly regulated process that involves multiple organs and cell types. It plays a critical role in maintaining acid-base homeostasis, regulating blood ammonia levels, and preventing ammonia toxicity. Dysregulation of this process can lead to serious health consequences.
'"
Protein | Definition | Taxonomy |
---|---|---|
Solute carrier family 12 member 2 | A solute carrier family 12 member 2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P55011] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
bumetanide | amino acid; benzoic acids; sulfonamide | diuretic; EC 3.6.3.49 (channel-conductance-controlling ATPase) inhibitor | |
n-(4-methylthiazol-2-yl)-2-(6-phenylpyridazin-3-ylthio)acetamide | N-(4-methylthiazol-2-yl)-2-(6-phenylpyridazin-3-ylthio)acetamide: a KCC2 cotransporter antagonist | pyridazines; ring assembly |