Several urea transport proteins have been identified in humans, including the products of the SLC14A1 and SLC14A2 genes. Study of urea transmembrane transport processes had suggested relatively fast transport kinetics, indicative of channel proteins that can conduct a stream of urea molecules (1).
In 2009 the structure of a urea transport protein was described (2, 3). Structurally similar urea transport proteins (UT family) exist in bacteria, fungi, insects, and vertebrates including mammals. The first reported urea transport protein structure is for a bacterial protein, dvUT, of Desulfovibrio vulgaris. The reported protein structure indicates that the UT urea transporter family members operate by a channel-like mechanism and suggest how the structure of the channel pore allows for urea selectivity.
In humans, urea transport is particularly well studied in the context of kidney physiology. Medical physiology textbooks often use urea as an example of a solute that can rapidly cross red blood cell membranes. Normally, transmembrane gradients of urea do not exert much osmotic force on red blood cells because urea rapidly crosses the cell membrane and an imposed concentration gradient for urea across the membrane is rapidly lost. Some humans have mutation in the gene that codes for the UT-B protein and their red blood cells have reduced rates of urea transport. Update 2012: the structure of human UT-B protein has been reported.
In the article “Urearetics: a small molecule screen yields nanomolar potency inhibitors of urea transporter UT-B“, data are shown for urea-induced changes in red blood cell volume. Red blood cells in a hyperosmolar solution with 250 mM urea show some rapid cell shrinking due to osmotic water efflux, followed by cell swelling as urea rapidly moves into the cells through urea channels (Figure 2d: volume changes completed in about one second). The urea analog acetamide, which is transported by UT-B, was used for a red blood cell lysis (rupture) assay. Acetamide was selected because its equilibration across human red blood cell membranes is about 2-fold slower than water. For lysis, red blood cells were first loaded with acetamide, then a 10-fold outward gradient of acetamide was generated by diluting the loaded cells into a buffer with no acetamide. Acetamide gradients of more than 500 mM were needed to begin to see red blood cell lysis (Figure 2a). The data show that by inhibiting the UT-B urea transport protein it is possible for a transmembrane urea gradient to exert more osmotic stress on red blood cells.
Urea transport is also important in the pathophysiology of stomach ulcers. The bacterial pathogen Helicobacter pylori is able to survive in the acidic human stomach where it makes use of a pH-sensitive urea transport protein, UreI (4). Humans with H. pylori are at risk for peptic ulcer disease and stomach cancer (5).
Image credits. The image shows a cartoon representation of the molecular structure of a urea transport protein of the bacterium Desulfovibrio vulgaris from the Protein Data Bank.