Organic Chemistry

1048 CHAPTER 25 The Organic Mechanisms of the Coenzymes • Metabolism

The coenzyme form of vitamin is thiamine pyrophosphate (TPP). TPP is the

coenzyme required by enzymes that catalyze the transfer of a two-carbon fragment

from one species to another.

Pyruvate decarboxylase is an enzyme that requires thiamine pyrophosphate.

Pyruvate decarboxylate catalyzes the decarboxylation of pyruvate and transfers

the resulting two-carbon fragment to a proton, resulting in the formation of acet-

aldehyde.

You may wonder why an acid such as pyruvate can be decarboxylated, since

the electrons left behind when is removed cannot be delocalized onto the

carbonyl oxygen. We will see that the thiazolium ring of the coenzyme provides a site

for the delocalization of the electrons. A site to which electrons can be delocalized is

called an electron sink.

Mechanism for Pyruvate Decarboxylase

The hydrogen bonded to the imine carbon of TPP is relatively acidic

because the ylide carbanion formed when the proton is removed is stabilized by the

adjacent positively charged nitrogen. The ylide carbanion is a good nucleophile.

In the first step of the mechanism for pyruvate decarboxylase, the nucleophilic

carbanion attacks the electrophilic ketone group of the acid. The resulting

intermediate can easily undergo decarboxylation because the electrons left behind

when is removed can be delocalized onto the positively charged nitrogen. The

positively charged nitrogen of TPP is a more effective electron sinkthan the

group of a acid, a class of compounds that are fairly easily decarboxylated

(Section 19.17). The product of decarboxylation is stabilized by electron delocaliza-

tion. One of the resonance contributors is neutral and the other has separated

charges—we will call it a resonance-stabilized carbanion. Protonation of the reso-

nance-stabilized carbanion and a subsequent elimination reaction form acetaldehyde

and regenerate the coenzyme.

b-keto

b-keto

CO 2

a-keto

NS

C

H

thiazolium ring

+ pKa = 12.7

NS+ H+

ylide carbanion

+ C

−

(pKa=12.7)

CO 2

a-keto

pyruvate

an -keto acid

O

CH 3 C

acetaldehyde

+ H+ H + CO 2

OO

CH 3 CCO− pyruvate decarboxylase

N

NH 2

NS

C

N

thiamine pyrophosphate

TPP

CH 2

H 3 C

H 3 CCH 2 CH 2 O

+

O

O−

PO

O

O−

PO−

H

Thiamine pyrophosphate (TPP) is B 1
required by enzymes that catalyze the
transfer of a two-carbon fragment from
one species to another.

Tutorial:

Mechanism for pyruvate

decarboxylase