Kinetics of hexokinase D ('glucokinase') with inosine triphosphate as phosphate donor. Loss of kinetic co-operativity with respect to glucose.
When ATP, the normal phosphate donor for hexokinase D ('glucokinase'), is replaced by ITP, the positive co-operativity with respect to glucose disappears. This may be rationalized in relation to kinetic models for hexokinase D co-operativity, which assume that with the normal substrates the chemical reaction and subsequent release of products occur so rapidly that binding of substrates cannot approach equilibrium and is therefore not constrained by the thermodynamic requirement that the Hill coefficient for substrate binding cannot exceed the number of binding sites. ITP is a much poorer substrate than ATP, however: its Km value at high glucose concentrations is 24 times the value for ATP, whereas the value of the limiting rate V is decreased about 8-fold. Consequently it is no longer possible for the ternary complex to be converted into products rapidly enough to generate kinetic co-operativity. The negative co-operativity with respect to glucose observed in 2H2O with ATP as phosphate donor also disappears when ITP is used instead of ATP.
Pollard-Knight
D
D
Department of Biochemistry, University of Birmingham, U.K.
Cornish-Bowden
A
A
D000818:Animals; D003903:Deuterium / Q000378:metabolism; D004187:Disaccharides / Q000378:metabolism*; D005941:Glucokinase / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D007292:Inosine Nucleotides / Q000378:metabolism*; D007293:Inosine Triphosphate / Q000378:metabolism*; D007700:Kinetics; D051381:Rats
D004187:Disaccharides; D007292:Inosine Nucleotides; C053880:2-acetamido-2-deoxy-3-O-(gluco-4-enepyranosyluronic acid)glucose; D007293:Inosine Triphosphate; C036863:magnesium ITP; D003903:Deuterium; D005941:Glucokinase; D005947:Glucose