Urea Transporter

Urea Transporter Uric Acid Uricostatic Drug Uricosuric Drug Urodilatin... 

Walsh, P. J., Wang, Y., Campbell, C. E., De Boeck, G., and Wood, C. M. (2001). Patterns of nitrogenous waste excretion and giU urea transporter mRJSTA expression in several species of marine fish. Mar. Biol. 139, 839-844. 

DUR3 Plasma membrane urea transporter, expression is highly sensitive to nitrogen catabolite repression and induced by allophanate, the last intermediate of the allantoin degradative pathway... 

SLC14 (2) symporters Urea transporters UT Kidney and red cells... 

SLC14 Urea transporter 2 Kidd antigen blood group... 

FIGURE 29—4 Mechanisms by which vasopressin increases the renal conservation of water. IMCD, inner medullary collecting duct TAL, thick ascending limb VRUT, vasopressin-regulated urea transporter. Thick and thin arrows denote major and minor pathways, respectively. 

Other renal actions mediated by receptors include increased urea transport in the inner medullary collecting duct and increased Na+ transport in the thick ascending limb both effects contribute to the uiine-concentrating abihty of the kidney (Figure 29-4). receptors also increase Na+ transport in the cortical collecting duct, which may synergize with aldosterone to enhance Na+ reabsorption during hypovolemia. 

In 2012, Verkman and coworkers identified a new class of triazolo-thienopyrimidine compounds as potent and metabolically stable inhibitors of kidney urea transporter UT-B. They synthesized these compounds via direct amination of the tautomerizable heterocycle using PyBOP in the presence of DBU in MeCN under microwave condition at 100°C (12JASN1210,13BMCL3338,12JMC5942). 

Sands JM. (1999) Regulation of renal urea transporters. JASN. 10(3) 635-646. 

Vasopressin also modifies the permeability of the collecting tubules to urea (but not to thiourea), which is transferred under the influence of the hormones from the tubular lumen into the interstitial tissue into the medulla where it contributes to the increase in the osmotic pressure. It is not known whether or not urea transport requires an active transport mechanism. 

The most likely explanation for the increase in urease activity seen with acidification is that there is a urea transporter in the bacteria. The urease gene cluster contains seven genes. There is a promoter followed by genes encoding the structural subunits, UreA and UreB. There is then a second promoter and then genes encoding Urel, -E, -F, -G, and -H. The last four are genes required for the assembly of active urease from the UreA-B apoenzyme by insertion of nickel, an essential cofactor in urease activity. UreE and -G and UreF and -H form heterodimers, and then a complex with UreA-B and nickel insertion occurs. 

Urel, however, encodes an inner membrane protein with six transmembrane segments and is likely to be the transporter that is acid activated, enabling urea access to intrabacterial urease. Hence, in the absence of activation of this urea transporter, urea has slow, bilayer permeability-determined access to the urease, and there is low activity of the urease above pH 6.5. With activation, there is a large increase in urea entry and, thus, increase in intrabacterial urease. 

When Urel is expressed in Xenopus oocytes, there is a large increase in urea uptake that is pH dependent. There is no increase at neutral pH but a large increase with acidification down to pH 4.0, the limit of survival of oocytes. The pH-transport curve can be overlaid on the pH-urease activity curve of intact bacteria. Half-maximal transport occurs at a medium pH of 5.9. The increased uptake is energy independent, temperature independent, and nonsaturable, properties indicating that Urel is a urea channel. This allows extremely fast transport of urea across the inner membrane of the bacteria. Complementation of Urel deletion mutants with wild-type Urel in H. pylori also restore urease activation at acidic pH, showing that Urel is a urea transporter in both the heterologous oocyte expression system and in the native organism. 

The Effect of Urel on Urea Transport in Xenopus Oocytes... 

Urel is probably the most important adaptation used by H. pylori for gastric colonization. This acid-activated urea transporter appears essential not only for survival in acidic media but also for survival in the stomach at its site of colonization. 

Acid activation of urea transport through the pH-gated urea channel Urel increases intrabacterial urease activity, and the ammonia produced buffers cytoplasm and periplasm. 

Table 9. Total Urea Fluxes Carrier-Assisted Urea Transport Through Supported Liquid Membranes, and (Adapted from ref. 69, 70) ...

Figure 2. Some of the transporters identified in the H. pylori genome. There are several other integral membrane proteins that are as yet functionally unclassified. The urea transporter is postulated based on data presented below.

The vast majority of the urease was found in intact bacteria, but was inactive until a medium pH of 6.5 was reached. As medium pH was lowered, there was a > 10-fold increase in urease activity that was maintained until a pH of 2.5 was obtained. A simple interpretation of these data is that there is activation of a urea transport at about pH 6.5 with an EC50 of pH 6 and that activation of this transport enables constant internal urease activity until a pH of 2.5 is reached [22]. 

These data show that the presence of urea and activation of urease by acidic medium pH enable acid survival of H. pylori. A model for the activation of internal urease by activation of a urea transport system is shown in Figure 8. 

At a medium pH >6.5, the urea transporter is inactive, and only surface urease modifies pH. Below pH 6.2, the transporter is activated and urea... 

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