Stabilization of rat liver tyrosine aminotransferase by tetracycline.
Rat liver tyrosine aminotransferase was purified 200-fold and an antiserum raised against it in rabbits. 2. Hepatic tyrosine aminotransferase activity was increased fourfold by tyrosine, twofold by tetracycline, 2.5-fold by cortisone 21-acetate and ninefold by a combination of tyrosine and cortisol administered intraperitoneally to rats. 3. Radioimmunoassay with 14C-labelled tyrosine aminotransferase, in conjunction with rabbit antiserum against the enzyme, revealed that cortisol stimulates the synthesis of the enzyme de novo, but that tetracycline has no such effect. 4. Incubation of rat liver homogenates with purified tyrosine aminotransferase in vitro leads to a rapid inactivation of the enzyme, which tetracycline partially inhibits. 5. The inactivation is brought about by intact lysosomes, and the addition of 10mM-cysteine increases the rate of enzyme inactivation, which is further markedly increased by 10mM-Mg2+ and 10mM-ATP. Here again tetracycline partially inhibits the decay rate, leading to the inference that the increase of tyrosine aminotransferase activity in vivo by tetracycline is brought about by the latter inhibiting the lysosomal catheptic action.
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D003348:Cortisone / Q000031:analogs & derivatives / Q000494:pharmacology; D003545:Cysteine / Q000494:pharmacology; D004789:Enzyme Activation; D006854:Hydrocortisone / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008247:Lysosomes; D008274:Magnesium / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D013752:Tetracycline / Q000494:pharmacology*; D014443:Tyrosine / Q000494:pharmacology; D014444:Tyrosine Transaminase / Q000302:isolation & purification / Q000378:metabolism*
D014443:Tyrosine; D000255:Adenosine Triphosphate; D014444:Tyrosine Transaminase; D013752:Tetracycline; D008274:Magnesium; D003545:Cysteine; D003348:Cortisone; D006854:Hydrocortisone