Organic Chemistry

1056 CHAPTER 25 The Organic Mechanisms of the Coenzymes • Metabolism

Once the amino acid has formed an imine with PLP, a bond to the can be

broken because the electrons left behind when the bond breaks can be delocalized onto

the positively charged protonated nitrogen of the pyridine ring. In other words, the

protonated nitrogen of the pyridine ring is an electron sink. If the OH group is re-

moved from the pyridine ring, the cofactor loses much of its activity. Apparently, the

hydrogen bond formed by the OH group helps weaken the bond to the

Mechanism for Decarboxylation

If the PLP-catalyzed reaction is a decarboxylation, the carboxyl group is removed

from the of the amino acid. Electron rearrangement and protonation of the

of the decarboxylated intermediate by a protonated amino group of a lysine

side chain or by some other acid group then reestablishes the aromaticity of the pyri-

dine ring. The last step in all PLP-requiring enzymes is a transimination reaction with

a lysine side chain, in order to release the product of the enzyme-catalyzed reaction

and regenerate enzyme-bound PLP.

Mechanism for Transamination

The first reaction in the catabolism of most amino acids is replacement of the amino

group of the amino acid by a ketone group. This is called a transaminationreaction be-

cause the amino group removed from the amino acid is not lost, but is transferredto the

ketone group of thereby forming glutamate. The enzymes that catalyze

transamination reactions are called aminotransferases. Transamination allows the amino

groups of the various amino acids to be collected into a single amino acid (glutamate) so

that excess nitrogen can be easily excreted. (Do not confuse transaminationwith

transimination, discussed previously.)

a-ketoglutarate,

a-carbon

a-carbon

a-carbon.

a-carbon

−O

O−

O

P

E

(CH 2 ) 4

CH 3

RCHCO−

PiO

Pi =

NH 2

O

transimination

PiOPiO

+N

H

+N

H

+N

H

N

HC

E

(CH 2 ) 4

CH 3

RCHCO− NH^2

O

N

HC

E

(CH 2 ) 4

CH 3

RCHCO−

NH

O

H

O

H

O

HC

NH

H

O

enzyme-bound PLP amino acid–bound PLP

transimination

O

with E (CH 2 ) 4 NH 2

N

H

RCH

+ CO 2

PiO

C

++

O−

E

N

H

(CH 2 ) 4 + RCH 2

+

+

NH 3

H

N

H

RCH

B

N

H

RCH 2

−B

mechanism for PLP-catalyzed decarboxylation of an amino acid

N

HC H

O

N

HC H

O

N

HC H

O

N

HC H

O

CH 3 CH 3 CH 3 CH 3

PiO PiO PiO