Thrombin Activatable Fibrinolysis Inhibitor (TAFI)

Carboxypeptidases (CPs) are important metabolic enzymes. They cleave off individual amino acids from the C-terminus of proteins being digested in the gut. The intestines are efficient in cleaving proteins down to their individual amino acids so they can be easily absorbed. The pancreas makes CPs along with other digestive enzymes, but a CP is also found in blood. So what business does a digestive enzyme like carboxypeptidase have in blood?

Carboxypeptidase B2 (CPB2), also known as carboxypeptidase U (CPU), plasma carboxypeptidase B (pCPB) or most commonly, thrombin-activatable fibrinolysis inhibitor (TAFI) is an important regulator of fibrinolysis, which is a highly orchestrated dissolution of a fibrin blood clot. This is the first step in the wound healing process. The clot is made mostly from fibrin, but it is not digested like proteins we consume. It is cleaved into small distinct fragments that are cleared from the circulation. So, again, what is a digestive enzyme doing in blood?

The answer is the nature of C-terminal lysine residues in proteins. Plasminogen, and its active form, plasmin has specific domains that bind proteins with C-terminal lysines. Additionally, plasminogen bound to proteins with C-terminal lysines is more readily activated to plasmin and plasmin prefers to cleave proteins after a lysine peptide bond. So in essence, plasmin is generating binding sites for itself and plasminogen. This is particularly important in fibrin dissolution.

Along with all the control mechanisms that regulate blood coagulation and fibrinolysis is a way to cleave off C-terminal lysines and limit the amount of plasmin and plasminogen binding sites on fibrin. Elevated or decreased TAFI levels have been associated with numerous hemostatic anomalies. [1-3 ].

Molecular Innovations TAFI ELISA kit can measure TAFI concentrations in plasma and serum from 2 ng/ml to 500 ng/ml.

Order Human TAFI ELISA Kit here.

References:

  1. Saes, J.L., et al. Journal of Thrombosis and Haemostasis, 16: 1498–1509, (2018).
  2. Bouma, B.N., & Meijers, J.C.M. Journal of Thrombosis and Haemostasis, 1(7), 1566-1574(2003).
  3. Chabloz, Patrick, et al. British journal of Haematology 115: 150-152 (2001).

Molecular Innovations also provides the following TAFI-related products:

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