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Enzymatic Redox Chemistry 127
H O
H R CH 3
CONH 2
Zn 2+
Zn 2+
Ser
H S
48 O
Ser
H O
H H H
48
O
R
H +
CH 3 H
N His 51
CONH 2
N
His 51
H S
R
N
N
H
Figure 6.6 Mechanism for alcohol dehydrogenase.
N+
R
N
H
Figure 6.7 Active site of horse liver alcohol dehydrogenase (PDB Wle 1HLD). Zn 2þ cofactor and
pentaXuorobenzyl alcohol substrate shown in black; NAD þ cofactor, Ser-48, and His-51 shown
in red.
Although hydride transfer might at Wrst sight seem unlikely in aqueous
solution, note that this transfer is occurring at close proximity within the
conWnes of an enzyme active site. There is also precedent for organic reactions
involving hydride transfer occurring in aqueous solution, such as the Cannizzaro
reaction shown in Figure 6.8.
Deuterium-labelling studies carried out on alcohol dehydrogenase have
established that the same hydrogen atom abstracted from ethanol is transferred
to the nicotinamide ring. It has also been established, using kinetic isotope
eVect studies, that there is a single transition state for the enzyme-bound