Elevated carbohydrate phosphotransferase activity in human hepatoma and phosphorylation of cathepsin D

Abstract

Summary To determine the cause of the increased content of carbohydrate-bound phosphate in tumour lysosomal hydrolases, the activity and kinetics in human hepatocellular carcinoma of two enzymes involved in the formation of mannose-6-phosphate in lysosomal hydrolases UDP-GlcNAc: lysosomal enzyme GlcNAca 1-phosphotransferase (GlcNAc-phosphotransferase) and phosphodiester glycosidase were studied. The activity level of the phosphotransferase with artificial and natural substrates was elevated (P<0.025 and P<0.001, respectively) in hepatoma compared to that in uninvolved tissue, while the phosphodiester glycosidase of hepatoma was at a level similar to that of the uninvolved tissue.To verify a previous observation that cathepsin D of human hepatoma contained increased GlcNAcphosphomannose, the protease was examined for carbohydrate phosphorylation by the GlcNAc-phosphotransferase. The protease from normal human liver was much more phosphorylated than hepatoma protease, confirming the previous observation. The predominant phosphorylation of the protease occurred in one of two major heavy subunits, with some phosphorylation in one of two minor light subunits.

Physiological effects of envenomation by two different doses of the viper Echis coloratusis crude venom on biochemical parameters in serum of Guinea pigs at different times.

“…In the present study, the levels of serum glucose were significantly increased after 1, 2 and 4 hours in the envenomated guinea pigs. The increases in serum glucose levels could be attributed to the effects of the venom on glycogen metabolism in the hepatocytes, muscle fibers and medullary catecholamines that stimulate glycogenolysis and gluconeogenesis in those tissues (Ohhira et al, 1991, Abdul-Nabi et al, 1997and March et al, 1997.…”

The Diversity of Bioactive Proteins in Australian Snake Venoms

“…This modification causes the lysosomal protein to bind mannose 6-phosphate receptors as part of the process of endocytosis and lysosomal targeting (61). Another example of a glycoprotein in which the carbohydrate moiety is phosphorylated is cathepsin D (62). Cathepsin D is an aspartic peptidase that is found at elevated levels in some tumor tissues; however, the role of the phosphorylated carbohydrate is unknown.…”

Inconsistent Expression of Glycolipid Sulfotransferase Activity between Hepatoma and Serum.

“…DISCUSSION Tumor-associated substances often leak into the sera of patients from tumor Glycolipid sulfotransferase activity of liver tissues and sera in chemically induced and uninduced LEA rats LEO rats and tissues, although the releasing mechanism is not necessarily understood in detail. This is also the case in such Golgi membrane-bound enzymes as /3-galactosyltransferase where the transmembrane domain is truncated (Podolsky et al 1977;Ueshima et al 1991), and N-acetyl-glucosaminylphosphotransferase (Ohhira et al 1991;Uehara et al 1991). Regarding GLST as well, there was an elevated serum enzyme level (Gasa et al 1990) in patients with renal cell carcinoma where the enzyme activity was markedly elevated (Sakakibara et al 1989).…”