The molecular basis for the accumulation of a substance which displays the immunological reactivity of α-1-antitrypsin within vesicles of liver parenchymal cells of individuals with hepatic cirrhosis and serum α-1-antitrypsin deficiency remains unclear. We recently reported that serum from a patient with α-1-antitrypsin deficiency and hepatic cirrhosis was substantially deficient in sialyltransferease (EC 126.96.36.199) an enzyme which transfers sialic acid from cytidine-5′-monophosphate-N-acetylneuraminic acid to a variety of asialoglycoprotein acceptors. In the present report we have extended these studies to include serum from five additional patients with α-1-antitrypsin deficiency and juvenile hepatic cirrhosis as well as a liver specimen obtained at autopsy of one of these patients. We find the sialytransferase activity in serum from six patients with α-1-antitrypsin deficiency and hepatic cirrhosis to be 50% of healthy pediatric control values and 30% of pediatric patients withliver disease. However, serum from family members homozygous for α-1-antitrypsin deficiency but without hepatic cirrhosis, and serum from patients with a variety of other kinds of liver disease, failed to exhibit the marked sialyltransferase deficiency. Similar assays carried out on a homogenate of a liver sample from one patient with α-1-antitrypsin deficiency and hepatic cirrhosis indicated that the deficiency of sialyltransferase activity was not demonstrable in liver. Furthermore, a comparative kinetic analysis of serum and liver sialyltransferase in normal and afflicted individuals failed to detect differences in substrate affinities which might account for a decrease in functional sialyltransferase capacity in individuais with α-1-antitrypsin deficiency and hepatic cirrhosis. These observations suggest that the serum sialyltransferase deficiency in such patients probably arises after chronic and extensive liver disease involving hepatic accumulation of α-1-antitrypsin rather than the enzyme deficiency being the primary cause of the hepatic cirrhosis and α-1-antitrypsin deficiency.
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