Human liver mRNA isolated from subjects phenotyped as homozygous PiMM or PiZZ α1‐antitrypsin, was translated in a reticulocyte cell‐free system, and α1‐antitrypsin identified by immunoprecipitation. In the presence of dog pancreas membranes the translated α1‐antitrypsin appeared as a larger product. Treatment with endo‐β‐N‐glucosaminidase yielded a protein smaller than the reticulocyte translated product, presumably due to removal of the N‐terminal signal sequence by membranes and sugar residues by endo‐β‐N‐glucosaminidase. Quantitation of α1‐antitrypsin translated from PiMM and PiZZ livers suggests that both mRNA species were present at the same cellular concentration, and that processing to the core glycosylation stage proceeded at identical rates.

mRNA was prepared from autopsy liver samples from a homozygote for a I-antitrypsin deficiency (PiZZ) and from a normal (PiMM) subject. Both preparations gave equivalent synthesis of CXI-antitrypsin in a wheat germ cell-free system. This suggests that the deficiency of plasma crl-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. atATsynthesis alA T deficiency Human liver mRNA

Microinjection of human liver mRNA from a patient homozygous for α1‐antitrypsin deficiency (PiZZ) into Xenopus oocytes led to a 2–10‐fold increase in lysosomal activity. Stimulation of lysosomal activity was not observed when mRNA from a normal human liver (α1‐antitrypsin PiMM), or water was injected into the oocyte. This lysosomal activity was oocyte derived and was not due to translation products of the human liver mRNA. Thus a protein that accumulates intracellularly in the secretory pathway is capable of stimulating lysosomal activity.