From Wikipedia, the free encyclopedia
Jump to navigation Jump to search
Coagulation factor XIII 1EVU.png
Transglutaminase example: coagulation factor XIII from human blood. PDB code: 1EVU.
EC number2.3.2.13
CAS number80146-85-6
IntEnzIntEnz view
ExPASyNiceZyme view
MetaCycmetabolic pathway
PDB structuresRCSB PDB PDBe PDBsum

Transglutaminases are enzymes that in nature primarily catalyze the formation of an isopeptide bond between γ-carboxamide groups ( -(C=O)NH2 ) of glutamine residue side chains and the ε-amino groups ( -NH3 ) of lysine residue side chains with subsequent release of ammonia ( NH3 ). Lysine and glutamine residues must be bound to a peptide or a protein so that this cross-linking (between separate molecules) or intermolecular (within the same molecule) reaction can happen.[1] Bonds formed by transglutaminase exhibit high resistance to proteolytic degradation (proteolysis).[2] The reaction is[1]

Gln-(C=O)NH2 + NH2-Lys → Gln-(C=O)NH-Lys + NH3

Transglutaminases can also join a primary amine ( RNH2 ) to the side chain carboxyamide group of a protein/peptide bound glutamine residue thus forming an isopeptide bond[1]

Gln-(C=O)NH2 + RNH2 → Gln-(C=O)NHR + NH3

These enzymes can also deamidate glutamine residues to glutamic acid residues in the presence of water[1]

Gln-(C=O)NH2 + H2O → Gln-COOH + NH3

Transglutaminase isolated from Streptomyces mobaraensis -bacteria for example, is a calcium-independent enzyme. Mammalian transglutaminases among other transglutaminases require Ca2+ ions as a cofactor.[1]

Transglutaminases were first described in 1959.[3] The exact biochemical activity of transglutaminases was discovered in blood coagulation protein factor XIII in 1968.[4]


reaction mechanism of tTG
The upper reaction shows how a transaminase combines with a glutamine residue, releasing ammonia, and then the combination reacts with the amine group of a lysine residue of another protein, setting the enzyme free again.

Eight transglutaminases have been characterised in humans. These TGases have a three or four-domain organization, with immunoglobulin-like domains surrounding the central catalytic domain. The core domain belongs to the Papain (CA clan) superfamily and uses a Cys-His-Asp catalytic triad.[2]

Name Gene Activity Chromosome OMIM
Factor XIII (fibrin-stabilizing factor) chain A F13A1 coagulation 6p25-p24 134570
Keratinocyte transglutaminase TGM1 skin 14q11.2 190195
Tissue transglutaminase TGM2 ubiquitous 20q11.2-q12 190196
Epidermal transglutaminase TGM3 skin 20q12 600238
Prostate transglutaminase TGM4 prostate 3p22-p21.33 600585
TGM X TGM5[5] skin 15q15.2 603805
TGM Y TGM6 unclear 20q11-15 613900
TGM Z TGM7 testis, lung 15q15.2 606776

Bacterial transglutaminases are single-domain proteins with a similarly-folded core. The transglutaminase found in some bacteria runs on a Cys-Asp diad.[6]

Transglutaminase, N-terminal, Ig E-set-like
SCOPed1ex0a1 / SUPFAM
Transglutaminase-like, core
SCOPed1ex0a4 / SUPFAM
Transglutaminase, C-terminal, Ig-like
SCOPed1ex0a2 / SUPFAM
Transglutaminase, bacterial

Biological role[edit]

Transglutaminases form extensively cross-linked, generally insoluble protein polymers. These biological polymers are indispensable for an organism to create barriers and stable structures. Examples are blood clots (coagulation factor XIII), as well as skin and hair. The catalytic reaction is generally viewed as being irreversible, and must be closely monitored through extensive control mechanisms.[2]

A collection of the transglutaminase substrate proteins and interaction partners is accessible in the TRANSDAB database.

Role in disease[edit]

Deficiency of factor XIII (a rare genetic condition) predisposes to hemorrhage; concentrated enzyme can be used to correct the abnormality and reduce bleeding risk.[2]

Anti-transglutaminase antibodies are found in celiac disease and may play a role in the small bowel damage in response to dietary gliadin that characterises this condition.[2] In the related condition dermatitis herpetiformis, in which small bowel changes are often found and which responds to dietary exclusion of gliadin-containing wheat products, epidermal transglutaminase is the predominant autoantigen.[7]

Recent research indicates that sufferers from neurological diseases like Huntington's[8] and Parkinson's[9] may have unusually high levels of one type of transglutaminase, tissue transglutaminase. It is hypothesized that tissue transglutaminase may be involved in the formation of the protein aggregates that causes Huntington's disease, although it is most likely not required.[2][10]

Mutations in keratinocyte transglutaminase are implicated in lamellar ichthyosis.

Industrial and culinary applications[edit]

Three bistro tenders being joined together with transglutaminase "meat glue". They will set overnight before being unwrapped, sliced into portions, cooked, and served.
Transglutaminase treated chicken terrine.

In commercial food processing, transglutaminase is used to bond proteins together. Examples of foods made using transglutaminase include imitation crabmeat, and fish balls. It is produced by Streptoverticillium mobaraense fermentation in commercial quantities (P81453) or extracted from animal blood,[11] and is used in a variety of processes, including the production of processed meat and fish products.

Transglutaminase can be used as a binding agent to improve the texture of protein-rich foods such as surimi or ham.[12]

So-called "Meat glue" made from bovine and porcine sources was banned throughout the European Union as a food additive in 2010.[13] Transglutaminase remains allowed and is not required to be declared, as it is considered a processing aid and not an additive which remains present in the final product.

Molecular gastronomy[edit]

Transglutaminase is also used in molecular gastronomy to meld new textures with existing tastes. Besides these mainstream uses, transglutaminase has been used to create some unusual foods. British chef Heston Blumenthal is credited with the introduction of transglutaminase into modern cooking.

Wylie Dufresne, chef of New York's avant-garde restaurant wd~50, was introduced to transglutaminase by Blumenthal, and invented a "pasta" made from over 95% shrimp thanks to transglutaminase.[14]

See also[edit]


  1. ^ a b c d e DeJong, GAH; Koppelman, SJ (2002). "Transglutaminase Catalyzed Reactions: Impact on Food Applications". Journal of Food Science. 67 (8): 2798–2806. doi:10.1111/j.1365-2621.2002.tb08819.x. ISSN 0022-1147.
  2. ^ a b c d e f Griffin M, Casadio R, Bergamini CM (December 2002). "Transglutaminases: nature's biological glues". The Biochemical Journal. 368 (Pt 2): 377–96. doi:10.1042/BJ20021234. PMC 1223021. PMID 12366374.
  3. ^ Clarke DD, Mycek MJ, Neidle A, Waelsch H (1959). "The incorporation of amines into proteins". Arch Biochem Biophys. 79: 338–354. doi:10.1016/0003-9861(59)90413-8.
  4. ^ Pisano JJ, Finlayson JS, Peyton MP (May 1968). "[Cross-link in fibrin polymerized by factor 13: epsilon-(gamma-glutamyl)lysine]". Science. 160 (3830): 892–3. Bibcode:1968Sci...160..892P. doi:10.1126/science.160.3830.892. PMID 4967475.
  5. ^ Aeschlimann D, Koeller MK, Allen-Hoffmann BL, Mosher DF (February 1998). "Isolation of a cDNA encoding a novel member of the transglutaminase gene family from human keratinocytes. Detection and identification of transglutaminase gene products based on reverse transcription-polymerase chain reaction with degenerate primers". The Journal of Biological Chemistry. 273 (6): 3452–60. doi:10.1074/jbc.273.6.3452. PMID 9452468.
  6. ^ Kashiwagi T, Yokoyama K, Ishikawa K, Ono K, Ejima D, Matsui H, Suzuki E (November 2002). "Crystal structure of microbial transglutaminase from Streptoverticillium mobaraense". The Journal of Biological Chemistry. 277 (46): 44252–60. doi:10.1074/jbc.M203933200. PMID 12221081.
  7. ^ Sárdy M, Kárpáti S, Merkl B, Paulsson M, Smyth N (March 2002). "Epidermal transglutaminase (TGase 3) is the autoantigen of dermatitis herpetiformis". The Journal of Experimental Medicine. 195 (6): 747–57. doi:10.1084/jem.20011299. PMC 2193738. PMID 11901200.
  8. ^ Karpuj MV, Becher MW, Steinman L (January 2002). "Evidence for a role for transglutaminase in Huntington's disease and the potential therapeutic implications". Neurochemistry International. 40 (1): 31–6. doi:10.1016/S0197-0186(01)00060-2. PMID 11738470.
  9. ^ Vermes I, Steur EN, Jirikowski GF, Haanen C (October 2004). "Elevated concentration of cerebrospinal fluid tissue transglutaminase in Parkinson's disease indicating apoptosis". Movement Disorders. 19 (10): 1252–4. doi:10.1002/mds.20197. PMID 15368613.
  10. ^ Lesort M, Chun W, Tucholski J, Johnson GV (January 2002). "Does tissue transglutaminase play a role in Huntington's disease?". Neurochemistry International. 40 (1): 37–52. doi:10.1016/S0197-0186(01)00059-6. PMID 11738471.
  11. ^ Köhler, Wim (22 August 2008). "Gelijmde slavink" (in Dutch). NRC Handelsblad. Archived from the original on 20 February 2009. Retrieved 5 March 2009.
  12. ^ Yokoyama K, Nio N, Kikuchi Y (May 2004). "Properties and applications of microbial transglutaminase". Applied Microbiology and Biotechnology. 64 (4): 447–54. doi:10.1007/s00253-003-1539-5. PMID 14740191.
  13. ^ "EU Bans 'Meat Glue' - Food Safety News". 24 May 2010. Archived from the original on 5 April 2018. Retrieved 6 May 2018.
  14. ^ Jon, Bonné (11 February 2005). "Noodles, reinvented". Archived from the original on 12 March 2008. Retrieved 2 April 2008.

Additional sources[edit]