Home >
Research Topics > Injectables Biomaterials/Tissue Engineering
TG Detail Section:
Transglutaminase (TG) enzymes are a family of enzymes that catalyze a posttranslational
acyl-transfer reaction between the γ-carboxamide groups of peptide-bound glutamine
residues and amines as shown in Scheme 1. Most TG enzymes are calcium-dependent and are
widely distributed in nature; several types have been identified in tissues, including
blood plasma, liver, hair follicle, skin, brain, eye lens, placenta, and other tissues.
Of these, TG enzyme extracted from blood plasma (Factor XIII) and from liver (tissue TG)
have been the most widely studied.
Scheme 1
A number of acyl acceptors (H2NR) have been identified, although in nature the acyl
acceptor is most commonly a peptide-bound lysine residue, resulting in the formation of ε-(γ-glutamyl)lysine protein crosslinks. The covalent peptide-peptide crosslinks
catalyzed by TGs are believed to impart mechanical stability as well as resistance to
chemical and enzymatic degradation to the protein assemblies upon which they act.
Factor XIII is the enzyme that catalyzes the last of a series of reactions during blood
coagulation, and circulates in blood plasma as a zymogen. Factor XIII is converted from
zymogen to active form (Factor XIIIa) upon cleavage of activation peptides by thrombin.
In the presence of Ca2+, Factor XIIIa catalyzes the formation of intermolecular
isopeptide bonds in fibrin following the action of thrombin on fibrinogen to form an
insoluble fibrin clot. Other soluble blood proteins, such as fibronectin, are also
known to participate in Factor XIII-mediated crosslinking. The primary biological role
of Factor XIII appears to be the mechanical stabilization of fibrin clots through the
formation of crosslinks between fibrin chains, and between fibrin chains and other
proteins in the clot and the extracellular matrix (ECM) of adjacent tissues.
Considerably less is known about the biological role of tissue TG, although it is widely
distributed in the cells and ECM of many tissues, which suggests that tissue TG plays a
role in crosslinking proteins in many physiologic and pathologic processes. These
include the crosslinking of membrane-bound proteins during cellular aging and programmed
cell death, wound healing and angiogenesis. Recently it was discovered that proteins
present in mineralizing cartilage and bone, such as osteonectin, osteopontin, and
collagen, are substrates for tissue TG, suggesting that tissue TG may also play a role
in bone matrix formation, mineralization and remodeling.
