Gluten triggers an immune response in those with coeliac disease. However, the mechanism by which it does this involves several other biochemicals. One of these, the enzyme transglutaminase 2 (TG2) which modifies the structure of gluten in the small intestine, may be able to be ‘turned off’ as a means to treat coeliac disease.
Stanford University researchers have investigated the TG2 enzyme, showing that it can be active or inactive depending on the forming or breaking of disulfide bonds between two amino acids in the enzyme. When TG2 is active, it can act upon gluten to change its structure and, in-turn, induce an overactive immune response.
Earlier, the team identified the enzyme that activates TG2 by breaking its disulfide bond. They have recently found an enzyme that re-forms this bond, inactivating TG2.
Previous studies in mice indicate the absence of TG2 does not negatively affect health. However, a lot of inactive TG2 has been found in the healthy small intestine, raising questions about its function in healthy people.
While considerably more research is still required, the latest findings indicate a pharmaceutical target to inactivate TG2 may be a promising future treatment for coeliac disease.
Reference: Yi et al, 2018. Journal of Biological Chemistry. DOI: 10.1074/jbc.RA117.001382
Article source: American Society for Biochemistry and Molecular Biology