Partial in vitro digestion of active gliadin-related peptides in celiac disease.
Peptides corresponding to residues 75-86 (RPQQPYPQPQPQ) and 75-85 of the A-gliadin structure, which were shown to be active in an animal model of celiac disease, were digested in vitro with small intestinal mucosa from children with celiac disease in remission and with mucosa from normal children. The products of digestion were separated into two fractions by gel permeation chromatography. Undigested residues (Mr > 400 fraction) from both peptides contained mainly glutamine, proline, and tyrosine, while the digested materials (Mr < 400 fraction) contained mainly proline, glutamine and arginine. Much larger amounts of undigested peptides were obtained from digestion with celiac mucosa than from normal mucosa. The results with peptide 75-86 indicated that the octapeptide 77-84 (QQPYPQPQ) was the main residual component and this peptide was shown to be active in the assay. Peptide 77-84 was also obtained as a residue from digestion of peptide 75-85, together with heptapeptide 77-83. The results lend further support for a primary mucosal defect in celiac disease and indicate that residual peptides in the small intestine of patients with the disease still retain appreciable toxicity.
Cornell
H J
HJ
Department of Applied Chemistry, RMIT University, Melbourne, Australia.
D000596:Amino Acids / Q000032:analysis / Q000378:metabolism; D000818:Animals; D002446:Celiac Disease / Q000378:metabolism*; D002642:Chick Embryo; D002648:Child; D004063:Digestion; D005903:Gliadin / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D010446:Peptide Fragments / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D012016:Reference Values; D017421:Sequence Analysis; D014443:Tyrosine / Q000378:metabolism