Molecular Pharmacology, Vol 6, 444-447, Copyright © 1970 by the American Society for Pharmacology and Experimental Therapeutics

Kinetics of Induction of Rat Liver Enzymes by Glucocorticoids

¹ Biochemistry Research Laboratory, Veterans Administration Center, Jackson, Mississippi 39216

The hypothesis that cortisone increases the synthesis of a group of rat liver enzymes to the same extent, and that their relative rates of accumulation are consequently determined by their respective degradative rate constants, is re-evaluated in terms of the original data and assumptions. The data do not for the most part conform to the changes in enzyme levels predicted by the kinetic model. A fundamental assumption upon which the original conclusions were based is shown to be erroneous; i.e., the initial rate of enzyme accumulation is not a valid estimate of the induced rate of enzyme synthesis. A rearrangement of the equation for enzyme accumulation permits calculation of the induced synthetic rate for any segment of the accumulation curve. Solutions of the equation are consistent with the concept of a lag period in the induction of tryptophan oxygenase (L-tryptophan:oxygen oxidoreductase, EC 1.13.1.12), tyrosine aminotransferase (L-tyrosine:2-oxoglutarate aminotransferase, EC 2.6.1.5), and alanine aminotransferase (L-alanine:2-oxoglutarate aminotransferase, EC 2.6.1.2) in adrenalectomized rats. Arginase (L-arginine amidinohydrolase, EC 3.5.3.1) was synthesized at a fairly constant induced rate from the earliest measured point in time, while the synthesis of alanine aminotransferase appeared to rise to a maximum at 1-2 days and then to decline to about half this value at the induced steady-state level. These kinetic analyses provide no support for the original hypothesis, or for the generalization that differences in accumulation rates of cortisone-induced enzymes are simply a function of their normal degradative rate constants.