Transglutaminase

Transglutaminase
Transglutaminase example: coagulation factor XIII from human blood. PDB code: 1EVU.
Identifiers
EC number	2.3.2.13
CAS number	80146-85-6
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Search PMC articles PubMed articles NCBI proteins

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 sperate 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]

Physiological transglutaminases

Eight transglutaminases have been characterised.^[2]

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.

Biological role

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

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.^[6]

Recent research indicates that sufferers from neurological diseases like Huntington's^[7] and Parkinson's^[8] 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][9]

Mutations in keratinocyte transglutaminase are implicated in lamellar ichthyosis.

Industrial and culinary applications

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 or extracted from animal blood,^[10] 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.^[11]

So-called "Meat glue" made from bovine and porcine sources was banned throughout the European Union as a food additive in 2010.^[12] 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

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.^[13]

See also

• Boneless Fish
• Surimi
• Bromelain
• Papain
• Ficain

References

Additional sources

• Kelleher, James B. (May 11, 2012). "Industry defends ingredient critics deride as "meat glue"". Chicago Tribune. Retrieved July 20, 2012.
• 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⁺