Metabolic pathway to 25-hydroxyvitamin D3-26,23-lactone from 25-hydroxyvitamin D3

mRNA was prepared from autopsy liver samples from a homozygote for α₁-antitrypsin deficiency (PiZZ) and from a normal (PiMM) subject. Both preparation gave equivalent synthesis of α₁-antitrypsin in a wheat germ cell-free system. This suggests that the deficiency of plasma α₁-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.