title: Altered alpha-mannosidase isoenzymes in the liver in hepatic cirrhosis.
abstract: Homogenates of liver from cases of hepatic cirrhosis due to alpha 1-antitrypsin deficiency (PiZZ) alcoholism were analyzed for their content of various lysosomal enzymes. Also determined were the specific activities of lactate dehydrogenase, glutamate-oxaloacetate transaminase, glutamate-pyruvate transaminase, and creatine phosphokinase in the extracts of liver from cases of both kinds of hepatic cirrhosis: all of these activities were within the range of control values. Similarly, the specific activities of the following lysosomal hydrolases were unremarkable: acid phosphatase, beta-mannosidase, beta-fucosidase, beta-glucuronidase and beta-glucosidase. Hexosaminidase specific activity was increased twofold in livers from the cases of cirrhosis due to alpha 1-antitrypsin deficiency. The specific activity of alpha-mannosidase (measured at pH 4.5) in homogenates of livers from PiZZ individuals with cirrhosis and those with alcoholic cirrhosis was increased two- to four-fold. Chromatography of the high-speed supernatant fraction from homogenates of livers of cirrhotic and noncirrhotic individuals on columns of DEAE-cellulose resolved alpha-mannosidase activity into two components: under the conditions employed, acid pH optimum (pH 4.5) alpha-mannosidase did not bind to the resin, whereas intermediate pH optimum (pH 5.5) alpha-mannosidase could be eluted with 0.1 mol/l NaCl. Liver from one case of (PiZZ) alpha 1-antitrypsin deficiency and emphysema, without demonstrable cirrhosis, was found to contain normal levels of both acid alpha-mannosidase and intermediate alpha-mannosidase. However, cases of cirrhosis due to alpha 1-antitrypsin deficiency contained twice as much acid alpha-mannosidase and only one third to one fourth as much intermediate alpha-mannosidase as controls. The deficiency in hepatic intermediate alpha-mannosidase was also observed in 5 of 5 cases of alcoholic cirrhosis.
mesh_terms: D006801:Humans; D006863:Hydrogen-Ion Concentration; D007527:Isoenzymes / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D008103:Liver Cirrhosis / Q000201:enzymology*; D008104:Liver Cirrhosis, Alcoholic / Q000201:enzymology; D008247:Lysosomes / Q000201:enzymology; D008361:Mannosidases / Q000378:metabolism*; D010641:Phenotype; D019896:alpha 1-Antitrypsin Deficiency; D043323:alpha-Mannosidase
chemical_list: D007527:Isoenzymes; D008361:Mannosidases; D043323:alpha-Mannosidase