Organic Chemistry

1026 CHAPTER 24 Catalysis

Overall Reaction

HO^

H HO^

H

H

OH

H

OH

H

B+

− (^2) O 3 POCH 2
− (^2) O 3 POCH 2
D-glucose-6-phosphate isomerase
D-glucose-6-phosphate D-fructose-6-phosphate
H OH O
OH
OH
HO OH
H
− (^2) O 3 POCH 2
CH 2 OH
6
5
4 1
3 2
H
O
H
HO
H
OH
OH
H
H
B B
H
B+
− (^2) O 3 POCH 2
CH 2 OH
O
H
H
H
OH
HO
OH
B B
O
C
H
B
− (^2) O 3 POCH 2
H
H
O
H
HO
H
OH
OH
H
H
B
+B
OH
C
H
B
− (^2) O 3 POCH 2
H
H
O
H
HO
O
OH
H
H
+BHB
CH 2 OH
H
B
− (^2) O 3 POCH 2
H
O
H
HO
O
OH
H
H
+B
B
in their cyclic forms, the enzyme must open the six-membered-ring sugar and convert
it to the five-membered-ring sugar. Glucose-6-phosphate isomerase is known to have
at least three catalytic groups at its active site, one functioning as a general acid and
two acting as general bases (Figure 24.11). The reaction proceeds as follows:

• The first step of the reaction is a ring-opening reaction. A general base (presum-
  ably a histidine residue) helps remove a proton, and a general acid (thought to be
  a lysine residue) aids the departure of the leaving group (Section 18.7).


• In the second step of the reaction, a base (apparently a glutamate residue) removes
  a proton from the of the aldehyde. Recall that are relatively
  acidic (Section 19.1).


• In the next step, the enol is converted to a ketone (Section 19.2).


• In the final step of the reaction, lysine acts as a general base to catalyze ring closure.

a-carbon a-hydrogens

Figure 24.11

Proposed mechanism for the isomerization of D-glucose-6-phosphate to D-fructose-6-diphosphate.