BIBC 120 Lecture Notes - Coeliac Disease, Intestinal Villus, Gliadin
24 May 2018
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Week 4.3
GLUTEN
- Gluten forms from the endosperm storage proteins gliadin and glutenin after
processing and mixing with water.
- Glute is i ay proessed foods iludig ie rea, soy saue, eer Glute Free
label must have < 20 PPM gluten.
- Celiac Disease
o Autoimmune disease of the small intestine (attack on mucosal enterocytes),
triggered by consuming gluten → lymphocyte infiltration and flattening of the
villi, destruction of intestinal villi leads to impaired nutrient absorption
(→nutrient deficiencies and weight lots)
o 1 out of every 133 Americans, difficult diagnosis
o Cause: Gliadins in gluten are hydrophobic proteins that contain large numbers of
proline (P) and glutamine (Q) AA, digestive proteases have lower activity cutting
where a proline resides on the carboxy side of the peptide bond (proline causes
a bend, lots of prolines → hard to cut)
▪ resistant to enzymatic hydrolysis (proline adds a bend to polypeptide
akoe so it’s diffiult to alig for atalyti leaage
▪ What causes the autoimmune reaction in Celiac Disease?
• Incomplete digestion of gliadin leaves polypeptides that are rich
in glutamine → polypeptides stimulate autoimmune response
▪ Tissue Transglutaminase (tTG)
• Enzyme that functions to modify glutamine residues in protein
and peptides
• gliadins have to get through enterocytes (somehow – in celiacs) to
cross link with tTG
• Found in various tissues throughout the body, including
enterocytes in mucosa of small intestine
• Found in both intracellular and extracellular (ECM) compartments
of these tissues
• Auto-antibodies target tTG in Celiac Disease; in brush-border
mucosa and potentially other sites in body
▪ Reactions catalyzed by tTG
• deaminate glutamine → glutamate (less likely)
• Gliadin peptide crosslinked to tTG (gliadin glutamine to tTG
lysine) (more likely)
o Explanation of autoantigen formation in celiac disease:
i. Gliadi peptides rossliked to tTG reatig e potetial auto-
atiges
ii. In people who are HLA-DQ2/8 (bind pieces of foreign proteins and
present them to T cells) genotype can potentially develop celiac disease
1. determines tissue type for transplant
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