Liver disease and serum hexosaminidase levels. Studies in a human hepatoma cell-line (Hep G2 cells).

Abstract

In various forms of liver disease, increased levels of the lysosomal enzyme beta-hexosaminidase (Hex) occur in serum. This may be caused by disturbances of the hepatocytic function, and we therefore studied the intracellular and extracellular isoenzyme pattern of Hex in a human hepatoma cell-line (Hep G2), using an immunoassay method, which separates Hex A and Hex B isoforms. This cell-line synthesizes and secretes Hex. The cumulative release of extracellular activity was about 3-10% of the intracellular activity. B-isoforms comprised one-third of intracellular activity but only 20% of extracellular activity. The proportion of extracellular B-isoforms increased with time, presumably due to instability of A-isoforms at 37 degrees C. Cycloheximide inhibited the release of Hex activity, whereas NH4Cl increased the extracellular fraction of Hex, even at a concentration of 1 mmol/l. We speculate that the increased concentration of NH4+ in patients with liver disease interferes with the distribution pathway of the lysosomal enzymes. This might be one reason for the increased serum Hex activity found in patients with liver disease.