Q.33 An enzyme has two binding sites for an inhibitor molecule. When the inhibitor binds to the
first site, the dissociation constant of the inhibitor for the second site increases, leading to
negative co-operativity. The Hill coefficient for such an inhibitor is
(A) equal to one (B) greater than one (C) less than one (D) less than zero
Negative cooperativity in inhibitor binding produces a Hill coefficient less than one due to decreased affinity at the second site. This makes option (C) less than one correct.
Hill Coefficient Fundamentals
The Hill coefficient (nH) quantifies cooperativity from binding curves: nH > 1 (positive), nH = 1 (non-cooperative), nH < 1 (negative).
Negative cooperativity occurs when first inhibitor binding reduces second site affinity (higher Kd), yielding a shallower saturation curve.
The Hill equation Y = [L]nH/(KA + [L]nH) fits data where nH < 1 reflects this reduced avidity.
Correct Answer: nH < 1
Option (C) less than one precisely describes negative cooperativity’s signature, confirmed by enzyme binding studies.
When first-site binding induces conformational change blocking second-site access, fractional saturation rises more gradually with [inhibitor].
Examples include glyceraldehyde-3-phosphate dehydrogenase with NAD+ showing nH ≈ 0.3-0.5.
Exam Application
Tests allosteric enzyme regulation understanding crucial for NEET/CSIR kinetics sections, distinguishing cooperativity types via plots.
Scatchard plots confirm negative cooperativity through concave-up curvature.
