Question

3. Microcalorimetric measurements of AH® and AS™ for the binding of captopril and lisinopril to ACE are shown in the following table. Conditions were 300 mM NaCl, 50 UM Zn2+, HEPES pH 7, 25° C. Thermodynamic constants for ACE-Inhibitor Association Inhibitor AH°, kJ/mol AS'', J/K mol 25.4 236.2 lisinopril 27.2 250.0 captopril a. Are these associations driven by enthalpy or entropy? Are they endothermic or exothermic? Justify your answers. b. Using these measurements, calculate the Ki for each of these inhibitors. c. Are the thermodynamically determined values of Ki consistent with the kinetically determined values? Explain. d. Considering the measurement conditions, propose an explanation for any significant differences between the thermodynamically determined values of Ki the kinetically determined values.

Answer 1

Thermodynamic equilibrium constant tells about the stability of a particular species over other....it means Gibbs free energy for that species is more negative compare to other one....

8.31 x 298 a Table shows AH values for both inhibitors are positive. It means it is endothermic Род. Tаkе also ѕhоux As' (htmp;) is also positive. Now we to know dog - du – TAS I for process dit is the and as is the Por spontaneous process do must be-ve which is only possible if dH is positive and as is highly positive also since only as is helping in making do (negative) therefore process is entropy duinen door dH - Tas I du captopril) - 25.4-298 * 2 3662 = -44,987647.000 we know dG = – RT Inkeg. - 44.9876 = - 8.31x298 in 1000 44987. 6 & 2.303 log bear 44987. 6 = log keq = 44987.6 8-31* 298*2.503 log keq = 7.888266 & Peqz 773153987 or beq Raptopril) = 107.88826 5703. 10314 For do •3 obril - 8.31 x 498x2 302 1000 Xlorn 47300 = log keq = 8.29 373042 5703-10314 8.29 37 3042 8 keq = 10 = 196666514 so key for Ceaptopril) is 1078 88266 and for (lisinopril) keg is 10843160 da li binobi) diº - rd so 8.2937302 = 27.2 – 298 × 250 -- 47.345 1000