As Substrates For Enzymes
Modification of Glutamine
Prolamins and to a lesser degree glutelins are excellent substrates for deamidation particularly by mammalian tissue transglutaminases (tTG). Deamidation is a process in which the R-C0-NH2 portion of glutamines (or asparagine) is hydrolyzed to R-CO-OH forming glutamic acid or aspartic acid. In gliadin the -QQP-, -QVP-, -QLP-, -QYP- tripeptides in the context of favorable adjacent peptides are readily deamidated. Most proteins have few or no such transglutaminase sites; however alpha gliadin has 13 such sites. Human tissue transglutaminase not only deamidates gliadin, but it also crosslinks itself to gliadin, which has immunological consequences. Gliadin also has a small peptide that appears to alter the distribution of transglutaminase in the gut but is not crosslinked, the mechanism of its 'innate' behavior is not clear. tTG also crosslinks gliadin to other proteins via these sites, generating anti-food responses, anti-self protein responses, and self-crossreactive responses to food proteins that result in secondary autoimmunities. The role of tTG in the extracellular matrix is to crosslink lysine side chains of proteins such as collagen to proteins, however glutens appear to infiltrate into the small intestine, interfering with this process and resulting in a false immune recognition of the matrix and surrounding cells as foreign, leading, ultimately, to the destruction of the intestinal mucosa. Seeds of certain plants may elicit the innate and cellular responses as a defensive response to overconsumption of seeds.
While prolamins and glutelins are excellent deamidase and transaminase substrates the highly repetitive motifs, particularly polyproline/glutamine tracts, are often poor substrates for gastroentestinal endoproteases, such as those produced in the GI tract. One clear example is a 33-mer of α-2 gliadin. Another digestion resistant region is a 25-mer which contains the innate peptide. The alpha gliadins, which bear these sites, specifically are poisonous to young rats when fed at concentrations higher than 1% and the addition of Mannosidase inhibitors increases the sensitivity specifically to alpha gliadins. These properties of certain alpha-gliadins appear to have evolved to prevent long-term or dedicated consumption of certain wheat grasses by certain species. This is one of the ironic properties of wheat, since a major advantage of wheat is the amount of protein in the wheat, however, some of this is wasted to the gut flora (or host immune system) since it cannot be broken down. One suggested remedy to this problem are new enzymes that help specifically break prolamins in the stomach. This may prevent the onset of wheat related disease in susceptible individuals, but no such screening is currently effective and once the clinical state is reached most individuals are so sensitive to wheat gliadins that, effectively, complete digestion in the stomach would be required.