Organic Chemistry

Section 25.4 Thiamine Pyrophosphate: Vitamin B 1 1049

PROBLEM 7

Draw structures that show the similarity between decarboxylation of the pyruvate–TPP in-

termediate and decarboxylation of a acid.

PROBLEM 8

Acetolactate synthase is another TPP-requiring enzyme. It also catalyzes the decarboxyla-

tion of pyruvate but transfers the resulting two-carbon fragment to another molecule of

pyruvate, forming acetolactate. This is the first step in the biosynthesis of the amino acids

valine and leucine. Propose a mechanism for acetolactate synthase.

PROBLEM 9

Acetolactate synthase can also transfer the two-carbon fragment from pyruvate to

forming This is the first step in the formation

of isoleucine. Propose a mechanism for this reaction.

Mechanism for the Pyruvate Dehydrogenase System
A compound must enter the citric acid cycle to be completely metabolized (Figure 25.1).
Thus, fats, carbohydrates, and proteins must be converted into compounds that are part
of the citric acid cycle or that can enter the cycle. Acetyl-CoA is the only compound

-ketobutyrate

O

CH 3 C

-aceto- -hydroxybutyrate

CCOO−

OH

CH 2 CH 3

+ CO 2

O O

+ CH 3 CH 2 C CO−

O O

CH 3 C CO−

acetolactate

synthase

TPP

a-ketobutyrate, a-aceto-a-hydroxybutyrate.

pyruvate

O O

CH 3 C

acetolactate

C

OH

CH 3

C O− + CO 2

O O

2 CH 3 C C O−

acetolactate

synthase

TPP

b-keto

CH 3

−B

H B

H

C

resonance contributor

resonance contributor

resonance-stabilized carbanion

mechanism for pyruvate decarboxylase

RN S

+

C

RN S

+ C

RN S

+

C

−

C−

RN S

+

C

−

RN S

+

C

O

C

CH 3 C

O

H

CH 3 C CH 3

O OH

H H+

H

O−

O

CH 3

C

RN S

+

C

OH

C O−

O

CH 3

C

RN S + CO 2

+

C

OH

B−

H B