Organic Chemistry

1046 CHAPTER 25 The Organic Mechanisms of the Coenzymes • Metabolism

In the first step of the flavin-catalyzed oxidation of an amino acid to an imino acid,

a basic side chain at the active site of the enzyme removes a proton from the

of the amino acid. The carbanion that is formed attacks the N-5 position of the flavin

ring. Collapse of the resulting tetrahedral intermediate gives the oxidized amino acid

(an imino acid) and the reduced coenzyme

Notice that FAD is a more versatile coenzyme than Unlike which

always uses the same mechanism, flavin coenzymes can use several different mech-

anisms to carry out an oxidation. For example, we have just seen that when

FAD oxidizes dihydrolipoate, nucleophilic attack occurs on the C-4a position of

the flavin ring, but when it oxidizes an amino acid, nucleophilic attack occurs on

the N-5 position.

Cells contain very low concentrations of FAD and much higher concentrations of

This difference in concentration is responsible for a significant difference in

the enzymes (E) that use as an oxidizing agent and those that use FAD.

Generally, FAD is covalently bound to its enzyme and remains bound after being re-

duced to Unlike NADH, does not dissociate from the enzyme. It,

therefore, must be reoxidized to FAD before the enzyme can enter another round of

catalysis. The oxidizing agent used for this reaction is NAD+or O 2 .Therefore, an

FADH 2. FADH 2

NAD+

NAD+.

NAD+. NAD+,

(FADH 2 ).

a-carbon

O

B H

B−

−B

S

H S

O

NH

N N

N

R

H 3 C

H 3 C

O

O

NH

N N

N

H

R

H 3 C

H 3 C

O

O

NH

H

N N

N

H

R

H 3 C

H 3 C

B H

S

R

S− S

H S R

R

mechanism for dihydrolipoyl dehydrogenase

dihydrolipoate lipoate

H B

R

H

NH

H 3 C N

N

H B

B H B H

H 3 C N O

O

R

NH

H 3 C N

N

B −

H

H 3 C N

NH 2

O

O

B −

B −

B −

NH 2

R

NH

H 3 C N

N

H

H

H 3 C N O

O

−

R C COO−

R C COO−

R C COO−^

R C COO−

NH 2

mechanism for D- or L-amino acid oxidase

+NH

NH 2

HB + R C COO− +

an amino acid

an imino acid