Introduction to Enzyme and Coenzyme Chemistry - E-Library Home

220 Chapter 9
S
− B 1 Enz
H
− CO 2
EnzB 2
−
S
H
CO 2
−
S
CO 2
−
NH +
NH
2− O 3 PO
+
N
H
OH
2− O 3 PO
N
H
OH
2− O 3 PO
N
H
OH
EnzB 2
NH + NH + NH +
CO −
2 CO − displacement
2
by Lys-NH 2
NH 2 NH
+
2
PLP
H 2 O
2− O 3 PO
CO −
2
+ NH 3
O
+
N
H
CO 2
−
OH
2− O 3 PO
H
N
H
CO 2
−
OH
Figure 9.14 Mechanism for methionine g-lyase.
9.5 Serine hydroxymethyltransferase
Serine hydroxymethyltransferase catalyses the interconversion of glycine and
l-serine, using PLP and tetrahydrofolate as cofactors. This enzyme is unusual
in that it utilises the PLP coenzyme for carbon–carbon bond formation.
The mechanism for this reaction is depicted in Figure 9.15, in the glycineto-serine
direction (the reaction is freely reversible). Following attachment of
glycine to the PLP cofactor, deprotonation generates a quinonoid intermediate
as seen above. However, this intermediate now reacts with N 5 -methylene tetrahydrofolate,
forming the carbon–carbon bond. A second deprotonation at the
a-position allows the elimination of the tetrahydrofolate cofactor, generating a
PLP–enamine adduct. This intermediate is attacked by water to generate the
hydroxymethyl side chain of l-serine.
This is an important cellular reaction, since in the reverse direction it can
be used to generate N 5 -methylene tetrahydrofolate from l-serine, and this
enzyme is largely responsible for the provision of cellular one-carbon methylene
equivalents.