Alpha 2-macroglobulin

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Alpha 2-macroglobulin

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Phone:617-632-7753

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Identifiers
Symbol A2M
Entrez 2
HUGO 7
OMIM 103950
RefSeq NM_000014
UniProt P01023
Other data
Locus Chr. 12 p13.31

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.

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:

Fibrinolysis (simplified). Blue arrows denote stimulation, and red arrows inhibition.
Fibrinolysis (simplified). Blue arrows denote stimulation, and red arrows inhibition.

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,[1][2] 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. 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.
  2. Kovacs DM (2000). "alpha2-macroglobulin in late-onset Alzheimer's disease". Exp Gerontol 35 (4): 473–9. PMID 10959035.

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Acknowledgement and Attribution Regarding Sources of Content

Some of the initial content on this page may be incorporated in part from copyleft sources in the public domain including wikis such as Wikipedia and AskDrWiki. Drug information for patients came from the The National Library of Medicine. Infectious disease information may have come from the Centers for Disease Control (CDC). Differential Diagnoses are drawn from clinicians as well as an amalgamation of 3 sources: 1.The Disease Database; 2. Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:3; 3. Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:7 .