Substrate and product inhibition initial rate kinetics of histone acetyltransferase.

Initial velocity and product inhibition kinetics of the histone acetyltransferase (EC 2.3.1.48) reaction indicate that the rat liver nuclear enzyme operates under a rapid equilibrium ordered bireactant mechanism. Histone adds first to the enzyme, and under the conditions of the experiment Ka = 0 as acetyl coenzyme A (CoA) concentration approaches saturating conditions. The Km for acetyl-CoA was 2.10 +/- 0.48 micrometer. Inhibition with acetyllysine resulted in a Kiq for the enzyme-acetyllysine complex of 1.96 +/- 0.30 mM. Inhibition with CoA yielded Kip for the ternary complex of 3.19 +/- 0.48 micrometer. These results indicate that the enzyme activity is comparatively independent of histone concentration, and, since the enzyme is sensitive only to acetyl-CoA and CoA concentrations, the enzyme will tend to maintain histones in the acetylated state.