title: Effects of protein-degradation inhibitors on the inactivation of tyrosine aminotransferase, tryptophan oxygenase and benzopyrene hydroxylase in isolated rat hepatocytes.
abstract: The following three potent inhibitors of hepatocytic proteolysis were investigated to see if they would inhibit the intracellular inactivation of enzymes: chymostatin and leupeptin (proteinase inhibitors) and methylamine (a lysosomotropic weak base). Chymostatin inhibited the inactivation of two of the three enzymes tested: tyrosine aminotransferase (EC 2.6.1.5) and tryptophan oxygenase (tryptophan 2,3-dioxygenase, EC 1.13.11.11). Leupeptin had no effect on any of the enzymes, whereas methylamine had only a weak inhibitory effect on tyrosine aminotransferase inactivation. Apparently proteolytic cleavage (probably by a non-lysosomal proteinase, since only chymostatin is effective) is involved in the inactivation of tyrosine aminotransferase and tryptophan oxygenase. The third enzyme, benzopyrene hydroxylase (flavoprotein-linked mono-oxygenase, EC 1.14.14.1), is probably inactivated by a non-proteolytic mechanism.
mesh_terms: D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors*; D001579:Benzopyrene Hydroxylase / Q000037:antagonists & inhibitors*; D002469:Cell Separation; D003513:Cycloheximide / Q000494:pharmacology; D066298:In Vitro Techniques; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007976:Leupeptins / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008744:Methylamines / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014366:Tryptophan Oxygenase / Q000037:antagonists & inhibitors*; D014444:Tyrosine Transaminase / Q000037:antagonists & inhibitors*
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007976:Leupeptins; D008744:Methylamines; D009842:Oligopeptides; C002101:chymostatin; D003513:Cycloheximide; C027451:methylamine; D014366:Tryptophan Oxygenase; D001579:Benzopyrene Hydroxylase; D001189:Aryl Hydrocarbon Hydroxylases; D014444:Tyrosine Transaminase; C032854:leupeptin