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  • Title: Alpha 2-macroglobulin and pregnancy zone protein. Serum levels, alpha 2-macroglobulin receptors, cellular synthesis and aspects of function in relation to immunology.
    Author: Petersen CM.
    Journal: Dan Med Bull; 1993 Sep; 40(4):409-46. PubMed ID: 7693397.
    Abstract:
    alpha 2-Macroglobulin, a 720 kDa tetramer, and Pregnancy Zone Protein, a 360 kDa dimer, are strongly homologous glycoprotein proteinase inhibitors of human plasma. alpha 2M and PZP monomers contain two regions of decisive functional importance i.e. the bait- and the thiol ester regions. The bait region serves as a substrate to a variety of proteinases, and cleavage in this domain causes a conformational change of the molecule. In addition, PZP forms tetramers when reacted with proteinase. As a result of the conformational change the thiol ester, which is hidden in the native structure, becomes readily accessible, and rapidly reacts with available nucleophiles preferably from the surface of the 'attacking' proteinase. The proteinase is thus covalently linked to alpha 2M/PZP but its active site is not affected. However, due to the structural changes in activated alpha 2M/PZP, bound proteinase is entrapped and its activity towards other than small substrates is sterically hindered. Presentation of receptor recognition sites (maximum four per tetramer) is also a consequence of reaction with proteinase. alpha 2M constitutes a large part of the plasma proteins and in early childhood serum contains as much as 4-5 g/l. Nearly all alpha 2M in the blood is native, since alpha 2M-proteinase complex is subject to rapid receptor-mediated clearance. The serum concentration in adults is about 2 g/l and shows little variation with age. The level is slightly higher in women than in men, and a modest (approximately 20%), possibly oestrogen induced, increase is observed during pregnancy. Sexual hormones, in particular androgens, might also account for the difference between childhood and adult alpha 2M levels. Yet, the reason for the downregulation during adolescence is not firmly established. In contrast to several of its animal homologues, human alpha 2M is not an acute phase protein. The serum level may change during acute and chronic disease, but the change is generally moderate and is not associated with any particular disease. Decreased alpha 2M concentration typically results from enhanced clearance of alpha 2M-proteinase complex and occurs in states of increased proteolytic activity, e.g. pancreatitis. Increased serum alpha 2M is frequently seen in nephrotic conditions and may mirror a change in plasma volume as well as in alpha 2M metabolism. Normal PZP serum levels are > 100 fold lower than those of alpha 2M. Male and female levels are similar in childhood, but unlike alpha 2M, PZP is strongly influenced by hormones.(ABSTRACT TRUNCATED AT 400 WORDS)
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