Transglutaminases

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Protein glutamine γ-glutamyl transferase
Identifier
Gene name (s) F13A1 , EPB42 , TGM1 , TGM2 , TGM3 , TGM4 , TGM5 , TGM6 , TGM7
External IDs
Enzyme classification
EC, category 2.3.2.13 ,  transferase
Response type Transfer of alkyl residues within or between proteins
Substrate Xaa-Gln-Xaa + Yaa-Lys-Yaa
Products Xaa-Glu (Xaa) -Lys (Yaa) -Yaa + NH 3
Occurrence
Parent taxon Eukaryotes , some bacteria

Transglutaminases (more precisely: protein-glutamine-γ-glutamyltransferases ) are enzymes that can create cross-links within or between proteins, which greatly changes the properties of the substrate. One example is the solidification of fibrin during blood clotting by factor XIII . Transglutaminases can be found in all eukaryotes ; eight such enzymes are known in humans, whose function, in addition to blood coagulation, is to stabilize various structural proteins . Mutations that lead to hereditary diseases are known from F13A1, EPB42, TGM1 and TGM5.

Most of the known transglutaminases from higher organisms are calcium- dependent, but calcium-independent bacterial transglutaminases (e.g. Streptomyces mobaraensis ) are also known which have no common origin with eukaryotic transglutaminases.

Catalyzed reaction

Transglutaminase catalyzes the acyl transfer from protein-bound glutamine residues to primary amines . If, in addition to the γ-glutamyl group of the amino acid glutamine, the ε-amino function of a protein-bound lysine residue is also involved in the reaction , an intra- or intermolecular crosslinking of proteins occurs through the formation of an isopeptide bond .

The cysteine (E-SH) in the active center of the transglutaminase initially reacts to form an acyl-S-enzyme complex, releasing ammonium ions. In the second step, the reamidation is carried out with an existing primary amine, releasing the enzyme again. The newly formed isopeptide bond is very stable from a biochemical point of view since it is not cleaved by proteases .

medicine

Tissue transglutaminase (transglutaminase 2, TG2) has become extremely important for the diagnosis of celiac disease . This food intolerance to cereal proteins leads to the formation of autoantibodies against the body's own tissue transglutaminase. The detection of this autoantibody (IgA anti-TG2 antibody) is the most important laboratory test for celiac disease (in addition to the detection of endomysial antibodies (EMA) of the IgA type); it is almost 100% negative predictive, its positive predictive value is approx. 72%.

Use as meat glue

An industrial application of transglutaminase is the cross-linking of proteins in sausage products and "restructured", i.e. H. Meat composed of different pieces (formed meat ) as well as fish and dairy products; the Ca 2+ -independent transglutaminase obtained from Streptomyces mobaraensis is used for this. The “molded meat product ” obtained in this way must be labeled as such or as Aliud (a product of its own); As a processing aid, however, transglutaminase has not yet been declared in the list of ingredients .

According to current food law, stricter regulations apply in Switzerland. Transglutaminase must be declared in the list of ingredients for all foods. In addition, the manufacturers are obliged to add the note "made from pieces of meat" to the product description.

Individual evidence

  1. ↑ EC  2.3.2.13
  2. ↑ Uniprot search result
  3. ↑ Swiss Institute of Bioinformatics (SIB): PROSITE documentation PDOC00473. Retrieved September 26, 2011 .
  4. ↑ Diagnosis and Therapy of Celiac Disease , Deutsches Ärzteblatt Online 2013, accessed on February 3, 2014
  5. ↑ Korponay-Szabó IR, Halttunen T, Szalai Z, et al. : In vivo targeting of intestinal and extraintestinal transglutaminase 2 by celiac autoantibodies . In: Good . 53, No. 5, May 2004, pp. 641-8. PMID 15082580 . PMC 1774023 (free full text).
  6. ↑ Lindfors K, Kaukinen K, Mäki M: A role for anti-transglutaminase 2 autoantibodies in the pathogenesis of celiac disease? . In: Amino Acids . 36, No. 4, April 2009, pp. 685-91. doi : 10.1007 / s00726-008-0127-5 . PMID 18594945 .
  7. ↑ Caputo I, Barone MV, Martucciello S, Lepretti M, Esposito C: Tissue transglutaminase in celiac disease: role of autoantibodies . In: Amino Acids . 36, No. 4, April 2009, pp. 693-9. doi : 10.1007 / s00726-008-0120-z . PMID 18600381 .
  8. ↑ Transglutaminase at the Bavarian State Office for Food Safety
  9. ↑ Ordinance on foods of animal origin. (PDF) Swiss Federal Office of Public Health, accessed on January 16, 2012 .