α2-macroglobulin (α2M)
alpha2-macroglobulin Quick Facts
- Molecular mass: 725 000 D
- Synthesis: Liver
- Half-Life: 2-3 days
Serum Concentration
| 11 days – 18 years | 2.7 – 5.4g/l 1.8 – 16kU/l |
| 19 years – 25 years | 1.4 – 4.1g/l 1.4 -12kU/l |
| 26 years – 61 years | 1.4 – 2.8g/l 1.4 – 4.8kU/l |
Normal range
| Activity | 99% ± 15% 0.70 – 1.50U/ml |
alpha2-macroglobulin Biochemistry
As a very unspecific inhibitor α2-macroglobulin inhibits proteases of all classes, including a variety of coagulation enzymes, such as thrombin, plasmin and kallikrein. The inhibitory activity is achieved by a so-called ‘bait region’ in the α2-macroglobulin molecule that is cleaved by the proteases. This results in a conformational change that captures the proteases in a type of cage. Alpha-2-macroglobulin may act as a carrier protein because it also binds to numerous growth factors and cytokines, such as platelet-derived growth factor, basic fibroblast growth factor, TGF-β, insulin, and IL-1β.
No specific deficiency with associated disease has been recognized, and no disease state is attributed to low concentrations of alpha-2-macroglobulin. The concentration of alpha-2-macroglobulin rises 10-fold or more in the nephrotic syndrome when other lower molecular weight proteins are lost in the urine. The loss of alpha-2-macroglobulin into urine is prevented by its large size. The net result is that alpha-2-macroglobulin reaches serum levels equal to or greater than those of albumin in the nephrotic syndrome, which has the effect of maintaining oncotic pressure.
α2-macroglobulin is the most important inhibitor of coagulation in newborns thus the plasma level is relatively high compared to adults.
Clinical Aspects of alpha2-mac
Reduced plasma concentrations have been observed during fibrinolytic therapy and in hyperfibrinolysis. Increased concentrations are observed during pregnancy, in women taking oral contraceptives, in the nephrotic syndrome, in diabetes mellitus and as a consequence of liver disease. Increased α2-macroglobulin concentrations in adults are of no clinical significance.
Clinical or Research use of alpha2-mac
Control of plasma concentration in newborns and small children, as α2-macroglobulin is the most important inhibitor of coagulation at this age.
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