In vitro synthesis of M and Z forms of human alpha 1-antitrypsin

Abstract

mRNA was prepared from autopsy liver samples from a homozygote for alpha 1-antitrypsin deficiency (PiZZ) and from a normal (PiMM) subject. Both preparations gave equivalent synthesis of alpha 1-antitrypsin in a wheat germ cell-free system. This suggests that the deficiency of plasma alpha 1-antitrypsin associated with the Z variant is due to a failure of processing and secretion of the protein rather than of its synthesis. It is likely that it is the resultant intracellular accumulation of the Z protein rather than a deficiency of protease inhibitor that is the primary cause of the liver pathology associated with this variant.