350
NUCLEOPHILIC REACTIONS INVOLVING ENOLATE ANIONS
increased stabilization in enolate anion
from 1,3-dicarbonyl compounds
pK a 20
pK a 9
H 3 C
CH 3
O
O
H 3 C
CH 3
O
O
H 3 C
CH 3
O
O
H
H
H
O
O
H
H
H
H
H
H
H
H
Box 10.1
Enols and enolization in the glycolytic pathway
Enols and enolization feature prominently in some of the basic biochemical pathways (see Chapter 15).
Biochemists will be familiar with the terminology enol as part of the name phosphoenolpyruvate, a metabolite of
the glycolytic pathway. We shall here consider it in non-ionized form, i.e. phosphoenolpyruvic acid. As we have
already noted (see Section 10.1), in the enolization between pyruvic acid and enolpyruvic acid, the equilibrium is
likely to favour the keto form pyruvic acid very much. However, in phosphoenolpyruvic acid the enol hydroxyl is
esterified with phosphoric acid (see Section 7.13.2), effectively freezing the enol form and preventing tautomerism
back to the keto form.
enolpyruvic acid
(enol ester)
OP =
phosphoenolpyruvic acid
pyruvic acid
hydrolysis of
phosphate ester
tautomerism
favours keto form
energy released is
coupled to ATP synthesis
ADP ATP
OP
CO 2 H
OH
CO 2 H
O
H 3 C
CO 2 H
O
P
O
OH
OH
Once the phosphate ester is hydrolysed, there is an immediate rapid tautomerism to the keto form, which
becomes the driving force for the metabolic transformation of phosphoenolpyruvic acid into pyruvic acid, and
explains the large negative free energy change in the transformation. This energy release is coupled to ATP
formation (see Box 7.25).
Tautomerism occurs elsewhere in the glycolytic pathway (see Section 15.2). The transformation of
glyceraldehyde 3-phosphate into dihydroxyacetone phosphate involves two such keto–enol tautomerisms, and
proceeds through an enediol.
H
OH
CH 2 OP
CH 2 OH
O
CH 2 OP
OH
CH 2 OP
OH
H
dihydroxyacetone
phosphate
D-glyceraldehyde
3-phosphate
keto−enol
tautomerism
enol−keto
tautomerism
common enol form
'enediol'
H
O
CHO
OH
H
HO
H
H
OH
H
OH
CH 2 OP
CH 2 OH
O
HO
H
H
OH
H
OH
CH 2 OP
D-glucose 6phosphate
D-fructose 6phosphate
aldose
ketose
OH
HO
H
H
OH
H
OH
CH 2 OP
common enol
OH
H
these sugar derivatives are
shown as Fischer projections to
represent stereochemistry
OP =
O
P
O
OH
OH
NUCLEOPHILIC REACTIONS INVOLVING ENOLATE ANIONS
increased stabilization in enolate anion
from 1,3-dicarbonyl compounds
pK a 20
pK a 9
H 3 C
CH 3
O
O
H 3 C
CH 3
O
O
H 3 C
CH 3
O
O
H
H
H
O
O
H
H
H
H
H
H
H
H
Box 10.1
Enols and enolization in the glycolytic pathway
Enols and enolization feature prominently in some of the basic biochemical pathways (see Chapter 15).
Biochemists will be familiar with the terminology enol as part of the name phosphoenolpyruvate, a metabolite of
the glycolytic pathway. We shall here consider it in non-ionized form, i.e. phosphoenolpyruvic acid. As we have
already noted (see Section 10.1), in the enolization between pyruvic acid and enolpyruvic acid, the equilibrium is
likely to favour the keto form pyruvic acid very much. However, in phosphoenolpyruvic acid the enol hydroxyl is
esterified with phosphoric acid (see Section 7.13.2), effectively freezing the enol form and preventing tautomerism
back to the keto form.
enolpyruvic acid
(enol ester)
OP =
phosphoenolpyruvic acid
pyruvic acid
hydrolysis of
phosphate ester
tautomerism
favours keto form
energy released is
coupled to ATP synthesis
ADP ATP
OP
CO 2 H
OH
CO 2 H
O
H 3 C
CO 2 H
O
P
O
OH
OH
Once the phosphate ester is hydrolysed, there is an immediate rapid tautomerism to the keto form, which
becomes the driving force for the metabolic transformation of phosphoenolpyruvic acid into pyruvic acid, and
explains the large negative free energy change in the transformation. This energy release is coupled to ATP
formation (see Box 7.25).
Tautomerism occurs elsewhere in the glycolytic pathway (see Section 15.2). The transformation of
glyceraldehyde 3-phosphate into dihydroxyacetone phosphate involves two such keto–enol tautomerisms, and
proceeds through an enediol.
H
OH
CH 2 OP
CH 2 OH
O
CH 2 OP
OH
CH 2 OP
OH
H
dihydroxyacetone
phosphate
D-glyceraldehyde
3-phosphate
keto−enol
tautomerism
enol−keto
tautomerism
common enol form
'enediol'
H
O
CHO
OH
H
HO
H
H
OH
H
OH
CH 2 OP
CH 2 OH
O
HO
H
H
OH
H
OH
CH 2 OP
D-glucose 6phosphate
D-fructose 6phosphate
aldose
ketose
OH
HO
H
H
OH
H
OH
CH 2 OP
common enol
OH
H
these sugar derivatives are
shown as Fischer projections to
represent stereochemistry
OP =
O
P
O
OH
OH