Alpha 2-macroglobulin

Alpha-2 macroglobulin (abbreviated α2M or A2M) is a large plasma protein found in the blood. It is produced by the liver, and is a major component of the alpha-2 band in protein electrophoresis.

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Structure

Alpha-2 macroglobulin is compose of four identical subunits bound together by -S-S- bonds.

Function

Alpha-2 macroglobulin is able to inactivate an enormous variety of proteinases (including serine-, cysteine-, aspartic- and metalloproteinases).

Alpha-2 macroglobulin has in its structure a 35 aminoacid "bait" region. Proteinases binding and cleaving the bait region become bound to α2M. The proteinase-α2M complex is recognised by macrophage receptors and cleared from the system.

It functions as an inhibitor of coagulation by inhibiting thrombin.^[1]

It functions as an inhibitor of fibrinolysis by inhibiting plasmin:

Disease

Alpha-2 macroglobulin levels are increased in nephrotic syndrome, a condition wherein the kidneys start to leak out some of the smaller blood proteins. Because of its size, α2-macroglobulin is retained in the bloodstream. Increased production of all proteins means α2-macroglobulin concentration increases. This increase has little adverse effect on the health, but is used as a diagnostic clue. Longstanding chronic renal failure can lead to amyloid by alpha-2 macroglobulin (see main article: amyloid).

A common variant (29.5%) (polymorphism) of α2-macroglobulin leads to increased risk of Alzheimer's disease,^[2][3] although the mechanism is unknown.

α-2 macroglobulin binds to and removes the active forms of the gelatinase (MMP-2 and MMP-9) from the circulation via scavenger receptors on the phagocytes.

References

1. ^ Boer JP, Creasey AA, Chang A, Abbink JJ, et al. (1993) "Alpha-2-macroglobulin functions as an inhibitor of fibrinolytic, clotting, and neutrophilic proteinases in sepsis: studies using a baboon model." Infect Immun. 61(12): 5035–5043.
2. ^ Blacker D, Wilcox MA, Laird NM, et al. (1998). "Alpha-2 macroglobulin is genetically associated with Alzheimer disease". Nat Genet 19 (4): 357–60. PMID 9697696.
3. ^ Kovacs DM (2000). "alpha2-macroglobulin in late-onset Alzheimer's disease". Exp Gerontol 35 (4): 473–9. PMID 10959035.