Urease regulation

The above methods of urease regulation relate to rapid changes in urease activity. Other means of regulation of urease have also been developed by the organism. Exposure to mild acidity increases urease assembly without changes... 

Peers, S., MiUigan, A., and Harrison, P. (2000). Assay optimization and regulation of urease activity in two marine diatoms. J. Phycol. 36, 523-528. 

The feedback-regulated drug delivery concept has been applied to the development of a bioerosion-regulated CrDDS by Heller and Trescony. " This CrDDS consists of a drug-dispersed bioerodible matrix fabricated from poly(vinyl methyl ether) half-ester, which was coated with a layer of immobilized urease (Fig. 26). In a solution with near neutral pH, the polymer only erodes very slowly. In the presence of urea, urease at... 

Fig. 26 Cross-sectional view of a bioerosion-regulated hydrocortisone delivery system, a feedback-regulated drug delivery system, showing the drug-dispersed monolithic bioerodible polymer matrix with surface-immobilized ureases. The mechanism of release and time course for the urea-activated release of hydrocortisone are also shown. (From Ref > 1)...

Urea is the most important end product of protein degradation in the body. Its concentration in blood depends on the protein catabolism and nutritive protein intake and is regulated by renal excretion. Thus the estimation of blood urea nitrogen is important in the assessment of kidney failure. The normal level of urea ranges from 3.6 mM to 8.9 mM. All enzymatic methods for urea determination are based on the principle of urea hydrolysis by urease ... 

Several structures of ureases are available (2). In all cases, the active site contains two Ni(II) ions bridged by the carboxylate group of a carbamylated lysine and by a hydroxide ion (Fig. lA). Each Ni is also coordinated by two histidines and one water molecule, whereas Ni(2) is further bound to an aspartate, resulting in a pentacoordinate Ni(l) and hexacoordinate Ni(2). In the resting state of the enzyme from Bacillus pasteurii, the active site accommodates a fourth water molecule, completing a tetrahedral cluster of solvent molecules (12). The access to the active site is regulated by a flexible helix-loop-helix motif, the position of other amino acids involved in the catalysis being also critically affected by the flap movement. 

Ureases [27] Niai)-Niai) Hydrolysis of urea Treatment of bacterial infections, regulation of nitrogen uptake in plants... 

A simplified model illustrating the means of regulation of intrabacterial urease activity is shown below, emphasizing the central role of Urel in this process. 

Figure 1. The general mechanism for ATP synthesis by aerobes and microaerobhiles. The environmental pH that is tolerated is pH 4 to 7. This pH is the same as that found in the periplasmic space unless there are specialized mechanisms for pH regulation such as urease. Over the range of pH from 4 to 7, various substrates are oxided via a series of electron acceptors which in turn are reoxidized by oriented redox complexes so that protons are exported electrogenically across the cytoplasmic membrane. This generates an interior negative potential and an inward pH gradient to provide the proton motive force for aerobic ATP S3mthesis and H gradient linked uptake or export of ions or solutes.

Overall, therefore, H. pylori behaves as a neutralophile and displays no evidence for direct adaptive mechanisms that would enable survival at the highly acidic pH that gastric contents must reach several times during the day. It is regulation of the periplasmic environment that is important for the organism rather than that of environmental pH, and for survival in stomach acid, rapid adaptive mechanisms must be present. The most important of these is urease activity. 

Figure 9. A model of the regulation of periplasmic pH by H pylori, showing acid-dependent activation of a uea transporter, activation of internal urease activity at a pH < 6.2 and thus maintenance of periplasmic pH at 6.2 and membrane potential at -105 mV...

Several other biosensors for pesticide and toxic metal monitoring are also based on the inhibition of enzymes such as urease for heavy metals, tyrosinase for benzoic acid, thiourea and 2-mercaptoethanol, alcohol dehydrogenase for cyanides and heavy metal salts, amino oxidase for plant growth regulators, aldehyde dehydrogenase for fungicides, cytochrome c for cyanides, catalase for heavy metals, and peroxidase for cyanides and heavy metals. Thus, biosensors based on the inhibition of enzymes, suffer from false-positive results. Despite lack of selectivity, this type of biosensor is powerful when rapid toxicity screening is required. 

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