Organic Chemistry

1060 CHAPTER 25 The Organic Mechanisms of the Coenzymes • Metabolism

Compare the second step in a PLP-catalyzed transamination with the second step in

a PLP-catalyzed racemization. In an enzyme that catalyzes transamination, an acidic

group at the active site of the enzyme is in position to donate a proton to the carbon at-

tached to the pyridine ring. The enzyme that catalyzes racemization does not have this

acidic group, so the substrate is reprotonated at the In other words, the

coenzymecarries out the chemical reaction, but the enzymedetermines the course of

the reaction.

Mechanism for Bond Cleavage

In the first step of the mechanism for PLP-catalyzed bond cleavage, a basic

group at the active site of the enzyme removes a proton from an OH group bonded to

the of the amino acid. This causes the bond to be cleaved. Serine

and threonine are the only two amino acids that can serve as substrates for the reac-

tion because they are the only amino acids with an OH group bonded to their

When serine is the substrate, the product of the cleavage reaction is

formaldehyde when threonine is the substrate, the product of the cleavage

reaction is acetaldehyde Electron rearrangement and protonation of the

of the amino acid, followed by transimination with a lysine side chain,

releases glycine.

The formaldehyde formed when serine undergoes bond cleavage never

leaves the active site of the enzyme; it is immediately transferred to tetrahydrofolate

(Section 25.8).

PROBLEM 14

Propose a mechanism for a PLP-catalyzed

Choosing the Bond to Be Cleaved

If all PLP-requiring enzymes start with the same substrate—an amino acid bound to

pyridoxal phosphate by an imine linkage—how can three different bonds be cleaved in

the first step of the reaction? The bond cleaved in the first step depends on the confor-

mation of the amino acid that the enzyme binds. There is free rotation about the

bond of the amino acid, and an enzyme can bind any of the possible confor-

mations about this bond. The enzyme will bind the conformation in which the over-

lapping orbitals of the bond to be broken in the first step of the reaction lie parallel to

the porbitals of the conjugated system. In this way, the orbital containing the electrons

left behind when the bond is broken can overlap with the orbitals of the conjugated

system. If such overlap cannot occur, the electrons cannot be delocalized into the con-

jugated system and the carbanion intermediate cannot be stabilized.

Ca¬N

a,b-elimination.

Ca¬Cb

a-carbon

(R=CH 3 ).

(R=H);

b-carbon.

b-carbon Ca¬Cb

Ca¬Cb

CA¬CB

a-carbon.

Tutorial:

Mechanism of PLP-dependent

reactions

O

transimination

glycine

O

RCH CH 2 CO−

O

CHCO−

O

O

+ RCH

O

CHCO−

E

(CH 2 ) 4

+ CH 2 CO−

+NH 3

B

N

H

H B

H

B

mechanism for PLP-catalyzed Cα C bond cleavage

with E (CH 2 ) 4 NH 2

+N

H

+N

H

+N

H

N

HC H

O

N

HC H

O

N

HC H

O

N
HC H
O
PiO

CH 3

PiO

CH 3

PiO

CH 3

PiO

CH 3