title: Amino acid composition of peptides remaining after in vitro digestion of a gliadin sub-fraction with duodenal mucosa from patients with coeliac disease.
abstract: Sub-fraction 9-2, derived from fraction 9 of a peptic-tryptic-pancreatinic digest of wheat gliadin and previously shown to be toxic to individuals with coeliac disease, was digested in vitro with duodenal mucosa from patients with coeliac disease in remission and with mucosa from normals. Digestion products from coeliac mucosa caused damage to rat liver lysosomes in contrast to digestion products from normal mucosa which had practically no effects on the lysosomes. Ion exchange chromatography of the digestion products, followed by gel permeation chromatography to remove tissue proteins and amino acids allowed the separation of small peptides. Purification of the peptide residues by reversed-phase HPLC on a C18 column resulted in four subfractions, two of which were cytotoxic to rat liver lysosomes. Amino acid analysis of these latter peptide fractions showed that they were both rich in glutamine/glutamic acid, proline, serine and tyrosine. The results support the hypothesis of defective mucosal digestion as being the aetiology of coeliac disease and suggest that the causative agents are small peptides of apparent Mr congruent to 700 Da, with amino acid analysis corresponding to (Glx)3, (Pro)2, Ser and (Glx)3, (Pro)2, Tyr. These hexapeptides are likely to be H-Pro-Ser-Glx-Glx-Glx-Pro-OH and H-Glx-Glx-Pro-Tyr-Pro-Glx-OH.
authors.affiliation: Royal Melbourne Institute of Technology, Australia.
authors.forename: H J
authors.initials: HJ
authors.lastname: Cornell
mesh_terms: D000596:Amino Acids / Q000032:analysis*; D002446:Celiac Disease / Q000473:pathology*; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D004386:Duodenum / Q000032:analysis*; D005903:Gliadin / Q000032:analysis*; D006801:Humans; D007413:Intestinal Mucosa / Q000032:analysis*; D010455:Peptides / Q000032:analysis*; D010940:Plant Proteins / Q000032:analysis*
chemical_list: D000596:Amino Acids; D010455:Peptides; D010940:Plant Proteins; D005903:Gliadin