Transglutaminase
A transglutaminase is an enzyme that catalyzes the formation of an isopeptide bond between a free amine group (e.g., protein- or peptide-bound lysine) and the acyl group at the end of the side chain of protein- or peptide-bound glutamine. The reaction also produces a molecule of ammonia. Such an enzyme is classified as EC 2.3.2.13. Bonds formed by transglutaminase exhibit high resistance to proteolytic degradation (proteolysis).
Transglutaminases were first described in 1959.[1] The exact biochemical activity of transglutaminases was discovered in blood coagulation protein factor XIII in 1968.[2]
Physiological transglutaminases
Eight transglutaminases have been characterised.[3]
| Name | Gene | Activity | Chromosome | OMIM |
|---|---|---|---|---|
| Factor XIII (fibrin-stabilizing factor) | F13A1, F13B | coagulation | 6p25-p24 | Template:OMIM2 |
| Keratinocyte transglutaminase | TGM1 | skin | 14q11.2 | Template:OMIM2 |
| Tissue transglutaminase | TGM2 | ubiquitous | 20q11.2-q12 | Template:OMIM2 |
| Epidermal transglutaminase | TGM3 | skin | 20q12 | Template:OMIM2 |
| Prostate transglutaminase | TGM4 | prostate | 3p22-p21.33 | Template:OMIM2 |
| TGM X | TGM5[4] | skin | 15q15.2 | Template:OMIM2 |
| TGM Y | TGM6 | unclear | 20q11-15 | Template:OMIM2 |
| TGM Z | TGM7 | testis, lung | 15q15.2 | Template:OMIM2 |
Mechanism of action
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.[3] A collection of the transglutaminase substrate proteins and interaction partners is accessible in the TRANSDAB database.
Role in disease
Deficiency of factor XIII (a rare genetic condition) predisposes to hemorrhage; concentrated enzyme can be used to correct the abnormality and reduce bleeding risk.[3]
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.[3] 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.[5]
Recent research indicates that sufferers from neurological diseases like Huntington's[6] and Parkinson's[7] 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.[3][8]
Mutations in keratinocyte transglutaminase are implicated in lamellar ichthyosis.
Industrial and culinary applications
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 or extracted from animal blood,[9] 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.[10]
Molecular gastronomy
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.[11]
See also
References
- ^ 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.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Pisano JJ, Finlayson JS, Peyton MP (1968). "[Cross-link in fibrin polymerized by factor 13: epsilon-(gamma-glutamyl)lysine.]". Science. 160 (3830): 892–3. doi:10.1126/science.160.3830.892. PMID 4967475.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ a b c d e Griffin M, Casadio R, Bergamini CM (2002). "Transglutaminases: nature's biological glues". Biochem J. 368 (Pt 2): 377–96. doi:10.1042/BJ20021234. PMC 1223021. PMID 12366374. Archived from the original on 20 April 2006.
{{cite journal}}: Unknown parameter|deadurl=ignored (|url-status=suggested) (help)CS1 maint: multiple names: authors list (link) - ^ Aeschlimann D, Koeller MK, Allen-Hoffmann BL, Mosher DF (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". J. Biol. Chem. 273 (6): 3452–60. doi:10.1074/jbc.273.6.3452. PMID 9452468.
{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - ^ Sárdy M, Kárpáti S, Merkl B, Paulsson M, Smyth N (March 2002). "Epidermal transglutaminase (TGase 3) is the autoantigen of dermatitis herpetiformis". J. Exp. Med. 195 (6): 747–57. doi:10.1084/jem.20011299. PMC 2193738. PMID 11901200.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Karpuj MV, Becher MW, Steinman L (2002). "Evidence for a role for transglutaminase in Huntington's disease and the potential therapeutic implications". Neurochem. Int. 40 (1): 31–6. doi:10.1016/S0197-0186(01)00060-2. PMID 11738470.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Vermes I, Steur EN, Jirikowski GF, Haanen C (2004). "Elevated concentration of cerebrospinal fluid tissue transglutaminase in Parkinson's disease indicating apoptosis". Mov. Disord. 19 (10): 1252–4. doi:10.1002/mds.20197. PMID 15368613.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Lesort M, Chun W, Tucholski J, Johnson GV (2002). "Does tissue transglutaminase play a role in Huntington's disease?". Neurochem. Int. 40 (1): 37–52. doi:10.1016/S0197-0186(01)00059-6. PMID 11738471.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Köhler, Wim (22 August 2008). "Gelijmde slavink" (in Dutch). NRC Handelsblad. Retrieved 5 March 2009.
{{cite news}}: Cite has empty unknown parameter:|coauthors=(help) - ^ Yokoyama K, Nio N, Kikuchi Y (2004). "Properties and applications of microbial transglutaminase". Appl. Microbiol. Biotechnol. 64 (4): 447–54. doi:10.1007/s00253-003-1539-5. PMID 14740191.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Jon, Bonné (11 February 2005). "Noodles, reinvented". MSNBC.com. Retrieved 2 April 2008.
Additional sources
- Kelleher, James B. (11 May 2012). "Industry defends ingredient critics deride as "meat glue"". Chicago Tribune. Retrieved 20 July 2012.
{{cite web}}: Italic or bold markup not allowed in:|publisher=(help) - U.S. patent 5,156,956 – A transglutaminase catalyzing an acyl transfer reaction of a Γ-carboxyamide group of a glutamine residue in a peptide or protein chain in the absence of Cz2+
External links