Gluten exorphins are peptides isolated from pepsin hydrolysates of wheat gluten. They have morphine-like opioid activity and can act like the body's own narcotics, the endorphins.1


Related Peptides

Four gluten exorphins were isolated from the enzymatic digest of wheat gluten and were named gluten exorphins:A5, A4, B5 and B4.2



Zioudrou et al. (1979) identified some opioid peptides in the digests of wheat prolamines with endorphin like activity and termed them “exorphins.” Fukudome and Yoshikawa (1992) have since characterized 15 separate amino acid sequences of gluten-exorphin A5 in a single molecule of wheat.1,2


Structural Characteristics

Gluten exorphins A5 (Gly-Tyr-Tyr-Pro-Thr), A4 (Gly-Tyr-Tyr-Pro), B5 (Tyr-Gly-Gly-Trp-Leu) and B4 (Tyr-Gly-Gly-Trp) were isolated from the enzymatic digests of wheat gluten. The structure-activity relationships of gluten exorphins A are unique. The presence of Gly at their N-termini increases their potency. Gluten exorphin B5, which corresponds to [Trp4,Leu5]- enkephalin, shows the most potent activity among these peptides.3


Mechanism of Action

In order for exorphins to function as opioid peptides in the central nervous system in vivo, they must (a) be produced in the gastrointestinal tract, (b) survive degradation by intestinal proteases, (c) be absorbed, without degradation, into the bloodstream, (d) cross the blood-brain barrier and thereby reach central opiate receptors, and (e) interact as opiates with these receptors.2



Gluten exorphins, which are exogenous opioids, bind to the same cellular receptors that endogenous opioids bind to, thus impacting on the immune system, nerve function, myelination processes, vascular walls, neuromuscular function, and a variety of CNS functions. Such opioids can have an anaesthetizing, analgesic, and addictive effect.1 




1.     Book: The book of Gluten by Stephen J Gislason, Gislason, Stephen J.

2.     Fukudome S, Yoshikawa M (1993). Opioid peptides derived from wheat gluten: their isolation and characterization. FEBS Letters, 316:17-19.

3.     Zioudrou C, Streaty RA, Klee WA (1979). Opioid peptides derived from food proteins. The exorphins. J. Biol. Chem. 254:2446-2449.

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