Regulation of Biodegradative Threonine Deaminase

The biodegradative threonine deaminase is subject to a marked inhibition by the reaction product, α-ketobutyrate, during the deamination of l-threonine when the reaction mixture lacks an effector, adenosine 5'-monophosphate. The addition of AMP to the reaction mixture at any stage during the reaction always results in an instantaneous activating or reactivating effect. Another reaction product, ammonia, has essentially no effect on the enzyme activity. The inhibition by α-ketobutyrate is characteristic in the following ways. It behaves as a competitive inhibitor with respect to the binding of AMP, and the degree of inhibition is more marked at low protein concentrations at which the tetrameric enzyme dissociates into a monomeric or a dimeric form. Furthermore, α-ketobutyrate itself can cause the enzyme to dissociate into its subunits, and conversely AMP counteracts this product-induced dissociation. Thus, the reaction product, α-ketobutyrate, appears to participate in regulating the enzyme as a kind of allosteric inhibitor, and at least one function of AMP activation is to prevent the inhibition by this product.