OK, time to post again. This one is a bit of a stand alone for those of us with food phobias which include gluten.
A zymogram is a very interesting tool, one I had never heard of until I received the pdf of this article via a friend in Scandinavia. It's from the same research group as discussed in this post. It's just a letter rather than a full research paper as the study is small, but possibly very important.
Anyway, a zymogram is an electrophoresis technique where an electric field is used to move a charged protein through a gel. It's used for hunting enzymes and what is special about the gel is that it contains the substrate for the enzyme you are hunting. If you bind gliadin in to the gel you can go hunting gliadinases in the gut contents of a human who does or does not have coeliac disease. Use your electric field to separate out the proteins and in the location where a hole gets burned in your gel, that's where a gliadinase is active. You can then work at characterising the gliadinase.
Here is a zymogram. The two ladders on the left are from normal people, there are no white bars. The next ladders have faint white bands where the gliadinases have eaten in to the gel. These are untreated coeliacs. The last lane, lane 5, has that massive burn out at 33kDa. This is a fully treated coeliac with no symptoms yet who has plenty of gliadinase in their gut.
Proline is an amino acid with a bent back. It's side chain is attached to it's amino group, putting a rigid bend in to a protein's structure. Apart from putting the essential tight twists in to collagen, proline also puts kinks in to gliadin. Lots of kinks. The sorts of kinks which stop gliadin fitting in to normal mammalian protein digesting enzymes. Particularly difficult to deal with are pairs of adjacent prolines. In fact there are only a handful of mammalian enzymes known which can act at this point. None of them fit the size/charge of the gliadinase found by Bernardo et al in their zymograms, at least one of which can do this. They think the enzyme is of bacterial origin. They only find it in the gut contents of people with coeliac disease.
It doesn't matter if you have active or diet controlled coeliac disease, the enzyme, and presumably the bacterium producing it is (pretty well) always and only present in coeliacs. So is coeliac disease an infection? Or are people with coeliac disease exquisitely good hosts for the gliadinase producing bacteria which do not establish in normal people?
This is fascinating. It's probably not the enzyme itself which is the trigger for coeliac disease (as pullulonase is for IBS) because it is detectable in controlled coeliacs as well as those with active disease. When there is no gliadin present to promote production of the enzyme it has to have other uses beyond splitting double prolines in gluten and it simply goes in to production overdrive when gliadin arrives. This seems likley.
If it's not the bacterium or the protease which trigger coeliac the other logical explanation is that the gliadinase is particularly good at producing immunogenic peptides from gliadin. This might be to do with the ability to split paired prolines, not something pancreatic lipase or brush border peptidases can do.
At the moment the only information available is observational. An intervention trial would eliminate the bacterium and its enzyme, check this on a zymogram, then re challenge with gliadin. We are probably years away from being able to try this but, if it turns out that this is a cure for coeliac disease, just think of the implications...
A genetic coeliac could eat real artisan breads, drink pints of Nelson's Revenge, freely eat pizza until having to buy a longer belt, develop hypothyroidism, get a wheelchair for gluten ataxia or multiple sclerosis... In fact all of the gifts of direct gluten consumption and toxicity (which probably don't need enzymic digestion to be received) could be shared by people who might have had to avoid gluten for digestive reasons! Share and share alike. We all need wheat.
Oh, except those of us who have contracted food phobias through dabbling in the scientific literature!
Hee hee, makes me think of "Three Men in a Boat" with pubmed substituting for the British Museum.