Organic Chemistry

enzyme that uses an oxidizing coenzyme other than may still require to
reoxidize the reduced coenzyme. For this reason, has been called the “common
currency”of biological oxidation–reduction reactions.

PROBLEM 4

Propose a mechanism for the reduction of lipoate by

PROBLEM 5 SOLVED

A common way for FAD to become covalently bound to its enzyme is by having a proton

removed from the C-8 methyl group and a proton donated to N-1. Then a cysteine or other

nucleophilic side chain of the enzyme attacks the methylene carbon at C-8 as a proton is

donated to N-5. Describe these events mechanistically.

SOLUTION

Notice that during the process of attaching FAD to the enzyme, FAD is reduced to

It is subsequently oxidized back to FAD. Once the coenzyme is attached to the

enzyme, it does not come off.

PROBLEM 6

Explain why the hydrogens of the methyl group bonded to flavin at C-8 are more acidic

than those of the methyl group bonded at C-7.

25.4 Thiamine Pyrophosphate: Vitamin

Thiamine was the first of the B vitamins to be identified, so it became known as vitamin
The absence of thiamine in the diet causes a disease called beriberi, which damages
the heart and impairs nerve reflexes. In extreme cases, it causes paralysis. One major di-
etary source of vitamin is the hulls of rice kernels (p. 1035). A deficiency is therefore
most likely to occur when highly polished rice is a major component of the diet. A
deficiency is also seen in alcoholics who are severely malnourished.

B 1

B 1.

B 1

FADH 2.

CysS−

FAD

O

O

NH

N N

N

H R H+

H 2 C

H 3 C

O

O

NH

H

N N

N

R

H 2 C

H 3 C

H+

O

O

NH

N N

N

R

H 3 C

O

enzyme-FAD enzyme-FADH 2

O

NH

H

N N

N

H

R

CysS CH 2

oxidation

H 3 C

CysS CH 2

B

B

B−

B−

B−

FADH 2.

+ Sox E

NAD+ NADH+ H+ FAD

E

FADH 2

E + Sred

FAD

NAD+

NAD+ NAD+

Section 25.4 Thiamine Pyrophosphate: Vitamin B 1 1047