**A. Inhibitor Constants of Porcine Citrate Synthase**The inhibitor constants for three inhibitors of porcine citrate synthase are summarized in the table below. The compounds were all determined to bind in the active site as competitive inhibitors of acetyl-CoA. Because they bind as competitive inhibitors, all three inhibitors must exhibit structural similarity to some part of acetyl-CoA. The compounds include:- **Bromoacetyl-CoA** with a $ K_i $ of 25.7 µM- **ATP** with a $ K_i $ of 6800 µM- **NADH** with a $ K_i $ of 8300 µMLook up in the textbook the structural formulas for Coenzyme A, ATP, and NADH. What is the largest structural fragment of each inhibitor that is responsible for competitive inhibition? Draw the molecular fragment common to each inhibitor that competes with the binding of acetyl-CoA in the active site of citrate synthase.**B. Relevance of Inhibitory Action in Vivo**While the inhibitor constants listed above were determined *in vitro* for purified citrate synthase, does their inhibitory action have any relevance to the flux of metabolites through the TCA cycle *in vivo*? If so, explain.

Answered: A. The inhibitor constants for three…

Biochemistry

9th Edition

ISBN:9781319114671

Author:Lubert Stryer, Jeremy M. Berg, John L. Tymoczko, Gregory J. Gatto Jr.

Publisher:Lubert Stryer, Jeremy M. Berg, John L. Tymoczko, Gregory J. Gatto Jr.

Chapter1: Biochemistry: An Evolving Science

Section: Chapter Questions

Problem 1P

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Question

**A. Inhibitor Constants of Porcine Citrate Synthase**

The inhibitor constants for three inhibitors of porcine citrate synthase are summarized in the table below. The compounds were all determined to bind in the active site as competitive inhibitors of acetyl-CoA. Because they bind as competitive inhibitors, all three inhibitors must exhibit structural similarity to some part of acetyl-CoA. The compounds include:

- **Bromoacetyl-CoA** with a $ K_i $ of 25.7 µM
- **ATP** with a $ K_i $ of 6800 µM
- **NADH** with a $ K_i $ of 8300 µM

Look up in the textbook the structural formulas for Coenzyme A, ATP, and NADH. What is the largest structural fragment of each inhibitor that is responsible for competitive inhibition? Draw the molecular fragment common to each inhibitor that competes with the binding of acetyl-CoA in the active site of citrate synthase.

**B. Relevance of Inhibitory Action in Vivo**

While the inhibitor constants listed above were determined *in vitro* for purified citrate synthase, does their inhibitory action have any relevance to the flux of metabolites through the TCA cycle *in vivo*? If so, explain.

Expert Solution

What inihibitor constants indicate?

Inhibitor constants are represented by

$for an enzyme catalysed reaction say : E + I \underset{K_{I}}{⇄} EI K_{I} = \frac{[I] [E]}{[EI]} where, [I] = is the conc . of inhibitor [E] = is the conc . of the free enzyme [EI] = is the conc . of the enzyme inhibitor complex .$

Ki is essentially the dissociation constant of a enzyme inhibitor complex. Therefore, lesser the dissociation constant more stronger the interaction of the inhibitor with the enzyme.

Considering the Ki values of bromoaceyl CoA, ATP and NADH; bromoaceyl CoA has the lowest Ki value. Therefore it is a better inhibitor.