Inactivation of yeast hexokinase B by triethyltin bromide.
Triethyltin bromide was found to demonstrate temperature-dependent inactivation of yeast hexokinase B. At temperatures of 20 degrees C or lower, little or no inactivation of the enzyme was detected after 2 h of reaction with 50-300 microM concentrations of the reagent. However, incubation at 25 degrees C or higher resulted in an increased rate and extent of loss of the enzyme activity with increasing incubation temperatures. The Arrhenius plot for the inactivation process showed a sharp break at approximately 30 degrees C, with a heat of activation (delta H*) above this temperature of 55.2 kcal, indicating that a triethyltin-induced conformational change occurred at the elevated temperatures. Sugar substrates provided protection against the inactivating effect by reducing the binding of triethyltin to the enzyme. In the absence of glucose, two sites of different affinity for triethyltin exist in the hexokinase monomer. Binding of triethyltin to the enzyme shifted its monomer-dimer equilibrium toward the monomeric form in an early stage of the interaction. Inactivation of the enzyme was associated with a slower subsequent event. Comparative effects of various organotin compounds on the activity of the enzyme indicated that inhibitory potency was associated with increasing hydrophobicity of the alkyl groups attached to the tin.
D000251:Adenosine Triphosphatases / Q000378:metabolism; D006593:Hexokinase / Q000037:antagonists & inhibitors*; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D007700:Kinetics; D009942:Organometallic Compounds / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D013329:Structure-Activity Relationship; D013696:Temperature; D013816:Thermodynamics; D014220:Trialkyltin Compounds / Q000494:pharmacology*; D014267:Triethyltin Compounds / Q000494:pharmacology*
D007527:Isoenzymes; D009942:Organometallic Compounds; D014220:Trialkyltin Compounds; D014267:Triethyltin Compounds; D006593:Hexokinase; D000251:Adenosine Triphosphatases; C026405:bromotriethylstannane