Re: what substances inhibit the activity of urease?

Dear Kevin,

Thanks for the question. As you will know, urease is produced by both plants and bacteria. The bacterium Helicobacter pylori, the well-studied gastric pathogen contains a particularly active urease which enables it to function in the acidic environment of the stomach and consequently, inhibition of urease is a hot topic in medical biology.

Due to this intensive study, a very large number of urease inhibitors are known. Rather than list them all here, I thought I'd point you to two excellent literature resources on the web:

http://www.biomednet.com/db/medl ine

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed

You have to register for the first one, but it's free. Type "urease and inhibition" as a query at either site and you'll get around 200 references!

The most important inhibitors fall into a number of groups. First there are metal ions-sodium, potassium, iron, copper and zinc. These work by competing for the metal binding site in urease, which contains nickel. Then there are reactive compounds that bind irreversibly to the cysteine residues found at the active site of urease. There are also chemicals such as phosphoramidate that bind to the nickel ion. A fourth major group of inhibitors are known as competitive inhibitors-these are molecules whose shape resembles urea and so can bind in the active site of the enzyme. Some of these include beta-mercapoethanol and cysteamine. Their effectiveness depends on how well the shape resembles that of the native substrate. One class of inhibitors that you will find in the literature are the hydroxamic acid derivatives, which have been widely studied as possible therapeutic agents.

Finally, specific antibodies to urease are of course inhibitory, as are certain small peptides that have been selected from random libraries. Of all the above-mentioned compounds, it's probably only antibodies produced in the immune response against H.pylori that could act against urease in the body-other inhibitory compounds in the body are probably present in too small concentrations to be effective.

Neil Saunders