Abstract
Gliadin, a glycoprotein present in wheat and other grass cereals, is a causative agent in coeliac disease. It is therefore important to find methods for the detoxification of gliadin. Lysosomal integrity is lost in patients with active coeliac disease but restored when gliadin is removed from the diet. We employed a rat liver lysosome assay to monitor the extent of detoxification of a gliadin digest by caricain, a protein enzyme found in papaya. Pre-incubating the gliadin digest for different durations with caricain allowed the kinetics of the detoxification process to be studied. A significant degree of protection (80%) of the lysosomes was achieved with 1.7% w/w of caricain on substrate after incubation for 2 h at 37 °C. The detoxification followed first-order kinetics with a rate constant of 1.7 x 10-4/s. The enzyme was strongly inhibited by imidazole, but weakly by phenylmethyl sulphonyl fluoride, as was also a caricain-enriched fraction from ion-exchange chromatography of papaya oleo-resin. The value of caricain in the detoxification of gliadin was confirmed in the present studies and this enzyme shows promise for enzyme therapy in coeliac disease.
Highlights
The use of enzyme therapy in coeliac disease depends upon choosing the most appropriate enzyme for detoxification of gluten-type proteins and understanding the way in which this enzyme can be evaluated.[1]
We took into account the pathogenic mechanisms operating in predisposed individuals and suggest that more complete digestion of gliadin peptides is essential in order to limit the concentration of specific immunogenic peptides that can trigger damage to tissue
We found that the same disruption occurred in vitro with rat liver lysosomes when treated with peptic-tryptic-pancreatic digests http://www.sajs.co.za
Summary
The use of enzyme therapy in coeliac disease depends upon choosing the most appropriate enzyme for detoxification of gluten-type proteins and understanding the way in which this enzyme can be evaluated.[1]. This work began with the use of peptic-tryptic-pancreatic digests of gliadin, representing a source of the most toxic peptides in wheat,[2] and focused on the toxicity of specific peptides in A-gliadin. This focus was made possible by the use of synthetic peptides within the A-gliadin sequence[3] and their evaluation using the foetal chick assay.[4]. The potential value of enzyme therapy was shown in a clinical trial[5] with 21 biopsy-proven volunteers with coeliac disease. There was evidence of improvement in villous architecture after enzyme therapy in three of these patients, even though they received a gluten challenge.[5]
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