Chirality in Biology
609
C
′
OOH
C
H
H
C
HOOC
OH
C
H
H
C
′′
OOH
COOH
C
H
S
H
R
C
HOOC
OH
C
H
R
H
S
COOH
pro-
R
pro-
S
HO
OH
O
H
S
O
HO
COOH
H
S
•
H
R
H
R
pro-
S
pro-
R
HO
OH
O
COOH
O
X
′′
O
X
′
HO
COOH
•
•
•
•
•
•
•
•
Fig. 20
Prochirality considerations for citric acid. The three structures at the
top show the assignments for the CH
2
COOH groups and the hydrogens of the
CH
2
groups; X
0
=
CH
2
C
0
OOH, X
00
=
CH
2
C
00
OOH; O
=
eye of observer. The
‘‘promoted’’ priority sequence is HO
>
COOH
>
CH
2
C
0
OOH
>
CH
2
C
00
OOH.
Derivations for H
R
and H
S
are not shown. The bottom line shows the action of
aconitase (citrate
→
H
2
O
+
cis
-aconitate) The H
R
proton (identiFed as
•
)is
removed from the pro-
R
methylene group.
Fig. 21
Alcohol dehydrogenase
stereochemistry. (a)
=
the reducing
cofactor, NADPH; R
1
=
rest of
structure, R
2
=
CONH
2
.TheH
A
(
=
H
R
)
hydrogen is transferred to form
(
S
)-[2-
2
H]-ethanol.
N
H
B
H
A
R
′′
R
′
O
CH
3
2
H
H
+
N
R
′′
R
′
H
A
H
B
OH
CH
3
2
H
H
OH
C
CH
3
H(
S
)
2
H
(a)
The ‘‘faces’’ or ‘‘sides’’ of trigonal car-
b
o
na
t
om
sc
a
na
l
s
ob
ed
i
s
t
i
n
g
u
i
s
h
e
d
.
For instance, the enzymatic reduction of
[1-
2
H]-acetaldehyde is stereospeci±c with
respect to the face of the carbonyl group
(Fig. 21). If the enzyme used is alcohol de-
hydrogenase, there is a further factor – the
two hydrogens at C-4 of the reducing coen-
zyme, NADH, are prostereoisomeric. They
are often described as H
A
and H
B
,co
r
-
responding respectively to H
R
and H
S
.
For citrate synthase, catalyzing the for-
mation of citrate from oxaloacetate and
acetyl-CoA, the ‘‘incoming’’ CH
2
COOH
unit, derived from acetyl-CoA, occupies
the pro-
S
position in citrate – the car-
bonyl of oxaloacetate was attacked from
only one side (Fig. 22). Stereochemical de-
scriptors to de±ne the sides and faces
of trigonal carbon atoms have been de-
vised; the specialist literature should be
consulted.
