Zinc as a modulator of transglutaminase activity – Laboratory and pathophysiological aspects

Abstract

For a whole century, citrate has been used as an in vitro anticoagulant via chelation of calcium. Later, also EDTA was introduced as an anticoagulant. An often overlooked fact is that zinc is bound to citrate and EDTA with affinities much greater than that for calcium, imposing problems in biomedical research. In vivo , proteins of the S100 family are released from leukocytes and known to bind calcium. Some of them, e.g., calprotectin, also chelate zinc. Thus, at an inflamed site, the ratio between Ca 2+ and Zn 2+ is changed. This mechanism is of importance for the modulation of the activation of a fascinating family of post-translationally acting calcium-dependent thiol enzymes, the transglutaminases, which are inhibited by zinc. This presentation illustrates the complexity of in vitro studies with zinc. Moreover, it exemplifies the role of Zn 2+ in pathophysiological situations such as celiac disease and neurodegeneration.

Zinc and gut microbiota in health and gastrointestinal disease under the COVID‐19 suggestion

“…Finally, zinc remains an interesting therapeutic option in celiac sprue according to its ability to up‐regulate TJs functioning and improve intestinal permeability to gliadin and other intraluminal antigens 81 (Table 3 ).…”

“…More interestingly, the TG2-thioester intermediatedeamidated gliadin complex could act as a "neo-antigen" and activate T-cells in "gluten sensitive and/or genetically predisposed" subjects. 80 Finally, zinc remains an interesting therapeutic option in celiac sprue according to its ability to upregulate TJs functioning and improve intestinal permeability to gliadin and other intraluminal antigens 81 (Table 3).…”