Organic Chemistry

Section 25.4 Thiamine Pyrophosphate: Vitamin B 1 1051

tions than are carboxylic acids (Section 17.20). At physiological pH (7.3), a carboxylic
acid would be present in its negatively charged basic form, which could not be
approached by a nucleophile.

PROBLEM 10 SOLVED

TPP is a coenzyme for transketolase, the enzyme that catalyzes the conversion of a ke-

topentose (xylulose-5-phosphate) and an aldopentose (ribose-5-phosphate) into an al-

dotriose (glyceraldehyde-3-phosphate) and a ketoheptose (sedoheptulose-7-phosphate).

Notice that the total number of carbon atoms in the reactants and products does not change

Propose a mechanism for this reaction.

SOLUTION The reaction shows that a two-carbon fragment is transferred from xylulose-

5-phosphate to ribose-5-phosphate. Because TPP transfers two-carbon fragments, we know

that TPP must remove the two-carbon fragment that is to be transferred from xylulose-

5-phosphate. Thus, the reaction must start by TPP attacking the carbonyl group of

xylulose-5-phosphate. We can add an acid group to accept the electrons from the carbonyl

group and a basic group to aid in the removal of the two-carbon fragment. The two-carbon

fragment, that becomes attached to TPP, is a resonance-stabilized carbanion that adds to

the carbonyl group of ribose-5-phosphate. Again, an acid group accepts the electrons from

the carbonyl group, and a basic group aids in the elimination of TPP.

H B

B −

CH 2 OPO 32 − CH 2 OPO 32 −

H O H

H OH

C OH

CH 2 OH

O

R

N

C

+

S

HO H

H OH

C

CH 2 OH

R

N

C −

+

S

15 + 5 = 3 + 72.

coenzyme A

CoASH

adenine

O

PO 32 −

OH

CH 2

O−

OOP

O

O− CH 3

CH 3 OH

P O C CH C NHCH 2 CH 2 C NHCH 2 CH 2 SH

OOO

CH 2

O

decarboxylated

cysteine

AMP pantothenate

xylulose-5-P

CH 2 OH

CH 2 OPO 32 −

CO

HO

H

H

OH

sedoheptulose-7-P

CH 2 OH

CH 2 OPO 32 −

CO

HO

H

H

OH

HOH

HOH

ribose-5-P

CH 2 OPO 32 −

HC O

H

H

H

OH

OH

OH

glyceraldehyde-3-P

transketolase

TPP

CH 2 OPO 32 −

HC O

HOH

+