Biochemistry
Biochemistry
9th Edition
ISBN: 9781319114671
Author: Lubert Stryer, Jeremy M. Berg, John L. Tymoczko, Gregory J. Gatto Jr.
Publisher: W. H. Freeman
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7. The compound below is a transition state analog that binds to the pyruvate dehydrogenase
enzyme complex (PDH) at the site for one of the five coenzymes used by the PDH. Binding is
significantly tighter (inhibitor constant K < 5 x 10-10 M) than the naturally occurring coenzyme
(inhibitor constant K, < 1x 10-5 M) indicating it fits the active site. Binding results in the
inactivation of the PDH.
NH2
CH3
H3C
N.
а)
List and draw the structure of this coenzyme.
Which of the coenzymes required by the PDH does this molecular analog displace?
transition state analog differ chemically from
b)
coenzyme?
How does
naturally occurring
b)
activity? This can be illustrated by drawing the reactions, in words, or both.
Why would the chemical difference, described in part b, result in a loss of PDH enzyme
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Transcribed Image Text:7. The compound below is a transition state analog that binds to the pyruvate dehydrogenase enzyme complex (PDH) at the site for one of the five coenzymes used by the PDH. Binding is significantly tighter (inhibitor constant K < 5 x 10-10 M) than the naturally occurring coenzyme (inhibitor constant K, < 1x 10-5 M) indicating it fits the active site. Binding results in the inactivation of the PDH. NH2 CH3 H3C N. а) List and draw the structure of this coenzyme. Which of the coenzymes required by the PDH does this molecular analog displace? transition state analog differ chemically from b) coenzyme? How does naturally occurring b) activity? This can be illustrated by drawing the reactions, in words, or both. Why would the chemical difference, described in part b, result in a loss of PDH enzyme
Expert Solution
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The given molecular analogue name is Thiamine thiazolone pyrophosphate. It is a transition state analogue. It has high affinity for pyruvate dehydrogenase.

Pyruvate dehydrogenase complex causes oxidative decarboxylation of pyruvate to acetyl CoA. It requires five co-factors:- TPP, lipoamide, FAD, NAD+ and coenzyme A.

Pyruvate + NAD++ CoA PDHAcetyl CoA + CO2 + NADH + H+

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