Alpha-2 macroglobulin

General Information

alpha-2-macroglobulin

A2M is the largest non-immunoglobulin protein in plasma (725 kilodaltons molecular weight), consisting of 4 polypeptide chains. Each polypeptide chain consists of approximately 35 amino acids and (like C3 C4 complement) contains a thioester domain. Alpha-2-macroglobulin A2M is a broad-spectrum inhibitor of endoproteases. It can inhibit (block) almost all types of serine, thiol, metallo-proteases and carboxyl-proteases.

Under normal conditions, the serum level of alpha-2-macroglobulin A2M is higher in women than in men, which is related to the influence of estrogens.

Alpha-2-macroglobulin A2M is an acute phase protein. Cytokines such as: TGF-beta, IL1, IL2, IL6, PDGF, FGF, VEGF bind to alpha-2-macroglobulin. It affects the synthesis of acute phase proteins in hepatocytes.

Alpha-2-macroglobulin A2M also inhibits coagulation by inhibiting thrombin and activated factor X (FXa). It also acts as an inhibitor of fibrinolysis by inactivating plasmin and kallikrein.

Alpha-2-macroglobulin A2M is involved in the mechanism of Alzheimer's disease because it is significantly involved in the deposition and degradation of beta-amyloid components.

In nephrotic syndrome, when the filtration of plasma proteins increases and their reabsorption decreases, alpha-2-macroglobulin molecules cannot pass through the kidney valves due to their large size, and its concentration in serum increases 10 times or more compared to normal.

Patients with proteolytic diseases, such as pancreatitis, have low concentrations of alpha-2-macroglobulin.