prolamins
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The storage proteins in grains that cause celiac disease — they survive digestion intact because the gut wasn't built to break them down.
Prolamins are a class of storage proteins found in cereal grains. Their name comes from their unusual amino acid composition: rich in proline (prol-) and glutamine (-amin). This composition is what makes them so problematic in celiac disease — the gut's protein-digesting enzymes (proteases) cannot fully break them down because proline-rich sequences are highly resistant to cleavage. Fragments survive the digestive process and reach the small intestine intact.
The Relevant Prolamins
| Grain | Prolamin | Notes |
|---|---|---|
| Wheat | Gliadin (+ glutenin) | gliadin is the primary disease driver |
| Barley | Hordein | Also triggers celiac |
| Rye | Secalin | Also triggers celiac |
| Oats | Avenin | Controversial; most patients tolerate pure oats — see oats |
| Maize, rice, millet, sorghum | (different storage proteins) | Safe for celiac patients |
Why They Cross the Gut Barrier
Normal protein digestion breaks proteins into small amino acids or dipeptides — too small to trigger immune reactions. Prolamins resist this, leaving fragments of 10–30 amino acids (peptides) intact. These peptide fragments:
- Activate zonulin release, loosening tight-junctions
- Cross the epithelial barrier via paracellular or transcellular routes
- Encounter tissue-transglutaminase which modifies them into more immunogenic forms
- Are presented to cd4-t-cells via hla-dq2-dq8 molecules
The Gliadin Sub-Story
Within gluten (the collective term for wheat's storage proteins), gliadin is the fraction most intensely studied as a celiac trigger. The alpha-gliadin peptide 33-mer (33 amino acids long) is particularly resistant to digestion and contains multiple T cell epitopes — it is considered the dominant disease-driving fragment.
Therapeutic Angle
Because prolamins survive normal digestion, one drug strategy is to introduce additional enzymes that can specifically cleave proline-rich sequences — this is the rationale behind glutenases.
Related Concepts
gliadin | tight-junctions | tissue-transglutaminase | hla-dq2-dq8 | glutenases | zonulin | causes
Referenced In
mechanism | causes | glossary | research_plan