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Isomerases 231
H S
H R
*
H
O
phenylpyruvate
tautomerase
OH
CO 2
−
CO 2
−
Figure 10.6 Phenylpyruvate tautomerase.
ketosteroid
isomerase
O HO O
H H* H H *
H
O
H
OH
* H R
H S
OH
*H
HO
H
H
OH
H
OH
OH
CH 2 OPO 2−
3
glucose-6-phosphate
phosphoglucose
isomerase
HO
H
H
OH
H
OH
OH
CH 2 OPO 3
2−
Figure 10.7 Ketosteroid isomerase and phosphoglucose isomerase.
O
HO H
H OH
H OH
CH 2 OPO 2−
3
fructose-6-phosphate
Two-step keto–enol isomerisations are involved in the mechanisms of a
number of isomerase enzymes. Ketosteroid isomerase (see Section 3.5) catalyses
the isomerisation of D-2-ketosteroid to D-3-ketosteroid through a dienol intermediate,
as shown in Figure 10.7. This reaction involves deprotonation by
an active site base Asp-38 and concerted protonation by Tyr-14 to generate
the dienol intermediate. Asp-38 then returns the abstracted proton to the
g-position to complete the isomerisation reaction.
There is also a family of aldose–ketose isomerases that catalyse the interconversion
of aldose sugars containing a C-1 aldehyde with ketose sugars
containing a C-2 ketone. Phosphoglucose isomerase catalyses the interconversion
of glucose-6-phosphate with fructose-6-phosphate, as shown in Figure
10.7. This reaction proceeds by abstraction of the C-2 proton to generate an
enediol intermediate, followed by return of the proton speciWcally at the proR
position of C-1. Intramolecular transfer of H is observed in both directions,
indicating that a single active site base is responsible.
10.4 Allylic isomerases
We have already met a few examples of allylic (or 1,3-) migrations: the
ketosteroid isomerase reaction illustrated in the previous section is eVectively