Liver disease and serum hexosaminidase levels. Studies in a human hepatoma cell-line (Hep G2 cells).
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.
Hultberg
B
B
Department of Clinical Chemistry, University Hospital, Lund, Sweden.
Floren
C H
CH
Isaksson
A
A
Jensen
E
E
D000643:Ammonium Chloride / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000201:enzymology*; D003513:Cycloheximide / Q000494:pharmacology; D054818:Hexosaminidase A; D054819:Hexosaminidase B; D006801:Humans; D007527:Isoenzymes / Q000097:blood / Q000187:drug effects / Q000378:metabolism*; D008113:Liver Neoplasms / Q000201:enzymology*; D013997:Time Factors; D014407:Tumor Cells, Cultured; D001619:beta-N-Acetylhexosaminidases / Q000097:blood / Q000187:drug effects / Q000378:metabolism*
D007527:Isoenzymes; D000643:Ammonium Chloride; D003513:Cycloheximide; D054818:Hexosaminidase A; D054819:Hexosaminidase B; D001619:beta-N-Acetylhexosaminidases