On the inactivation of hepatic tyrosine aminotransferase.
Tyrosine aminotransferase from frog liver requires no exogenous pyridoxal-5'-phosphate for maximum activity. The cofactor cannot be removed from the enzyme by dialysis as in the case of the rat enzyme. Pyridoxal phosphate also fails to elevate frog liver tyrosine aminotransferase activity in vivo. The enzyme activity decreases rapidly after administration of cycloheximide, which indicates that its turnover is rapid. These results strongly contradict the cofactor-dependent model of enzyme degradation. Rat and frog liver tyrosine aminotransferases are stable in neutral homogenates at 37 degrees C but are rapidly inactivated after addition of cysteine in millimolar concentrations. This effect is probably due to cystine formed during the incubation. The rates of inactivation of the different subforms of the enzyme in this system were identical. No membrane-bound system is needed for the inactivation by cystine. It is possible that the denaturation occurs by sulfide exchange. Fructose and glucose lower the enzyme activity in both rat and frog liver to an equal extent. This effect is not due to instability of the enzyme activity in both rat and frog liver to an equal extent. This effect is not due to instability of the enzyme in the presence of sugars of their metabolites. Theories on the inactivation of enzymes will be discussed in the light of the present results.
D000818:Animals; D001001:Anura; D003513:Cycloheximide / Q000494:pharmacology; D003545:Cysteine / Q000494:pharmacology; D003553:Cystine / Q000378:metabolism; D004794:Enzyme Repression; D004837:Epinephrine / Q000494:pharmacology; D005632:Fructose / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D008099:Liver / Q000201:enzymology*; D011732:Pyridoxal Phosphate / Q000494:pharmacology; D011896:Rana temporaria; D051381:Rats; D014444:Tyrosine Transaminase / Q000378:metabolism*
D005632:Fructose; D003553:Cystine; D011732:Pyridoxal Phosphate; D003513:Cycloheximide; D014444:Tyrosine Transaminase; D005947:Glucose; D003545:Cysteine; D004837:Epinephrine