Organic Chemistry

Section 25.3 Flavin Adenine Dinucleotide and Flavin Mononucleotide: Vitamin B 2 1045

FAD and FMN are oxidizing agents.

Mechanisms for Flavin Nucleotide Coenzymes
When FAD (or FMN) oxidizes a substrate (S), the coenzyme is reduced to (or
). and like NADH and NADPH, are reducing agents. All the
oxidation–reduction chemistry takes place on the flavin ring. Reduction of the flavin
ring disrupts the conjugated system, so the reduced coenzymes are less colored than
their oxidized forms.

PROBLEM 3

How many conjugated double bonds are there in

a. FAD? b.?

In the first step of the mechanism for the FAD-catalyzed oxidation of dihy-
drolipoate to lipoate, the thiolate ion attacks the C-4a position of the flavin ring.
This reaction is general-acid catalyzed—as the thiolate ion attacks the ring, a pro-
ton is donated to the N-5 nitrogen. A second nucleophilic attack by a thiolate ion,
this time on the sulfur that is covalently attached to the coenzyme, generates the ox-
idized product and Section 25.4 discusses where this FAD-catalyzed reac-
tion fits into metabolism.

FADH 2.

FADH 2

FAD

FMN

O

O

NH

+ Sred

N N

N

R

H 3 C

H 3 C

FADH 2

FMNH 2

O

O

NH

+ Sox

N

R

H 3 C

H 3 C

H

N

H

N

FMNH 2 FADH 2 FMNH 2 ,

FADH 2

O

+

succinate

−OCCH 2 CH 2 CO− FAD

fumarate

+ FADH 2

succinate

dehydrogenase

NADH + H+ + FMN NAD+ + FMNH 2

NADH dehydrogenase

CC

−OOC H

H COO−

O

O

+

dihydrolipoate

D-amino acid or

L-amino acid

CH 2 CH 2 CH 2 CH 2 CO−

O

FAD CH 2 CH 2 CH 2 CH 2 CO−

lipoate

+ FADH 2

dihydrolipoyl

dehydrogenase

SH SH SS

+

O

NH

RCCO−

O

NH 2

RCHCO− FAD + FADH 2

D-amino acid oxidase or

L-amino acid oxidase

FADH 2 and FMNH 2 are reducing agents.