Chirality in Biology
607
positions 67 and 95. The all-D and all-L pro-
teins were in every respect mirror images,
apart from enzymatic activity. They were
enantiospeciFc in cleavage of a hexapep-
tide analog of a normal cleavage site. The
all-D analog 2-aminobenzoyl-D-thr-D-ile-D-
nle-D-
p
-nitrophe-D-gln-D-arg(CONH
2
)was
cleaved only by D-enzyme; conversely, the
L-enzyme cleaved only the all-L hexapep-
tide (nle
=
norleucine).
In several cases, there are separate
enzymes for enantiomeric substrates; ex-
amples include D
-and L-amino acid oxi-
dases, D
-and L-lactate dehydrogenases, D-
and L-arabinose 1-dehydrogenases, and the
two 6-hydroxynicotine oxidases previously
noted. Such enzymes acting in concert
would provide a racemase possibility, for
example, for lactate dehydrogenases:
L-(+)-lactate
NAD
+
Pyruvate
NADH, H
+
D-(
)-lactate
NADH, H
+
NAD
+
In other cases, a single enzyme func-
tions as a racemase and is, therefore,
an example of an enzyme utilizing both
enantiomers. Racemase enzymes are es-
pecially well known for amino acids (e.g.
serine racemase noted earlier) and hy-
droxyacids (e.g. lactate, mandelate). An
important enzyme involved in propionyl-
CoA metabolism interconverts the (
R
)and
(
S
) forms of methylmalonyl-CoA (±ig. 18).
Although often termed
methylmalonyl-CoA
racemase
, this enzyme is technically not
a racemase since the Fve chiral centers
of
the
CoA
component
are
(presum-
ably) unchanged. The more appropriate
name is methylmalonyl-CoA epimerase
(EC 5.1.99.1).
6
Prostereoisomerism
Many enzyme substrates have the general
achiral structure, Caabc; there are two
chemically like atoms or groups of atoms,
a, and two different atoms or groups of
atoms, b and c. Although these structures
are achiral, the two a groups are in
different
stereochemical
environments.
±or convenience, the a groups will be
distinguished as
a
0
and a
00
.W
h
e
na
0
is observed as if to determine chirality
by the Cahn–Ingold–Prelog method, the
sequence a
00
b
c has a right-handed
sense (±ig. 19a). Similarly, with a
00
in the
remote position, the sequence a
0
b
c
has a left-handed sense (±ig. 19b). If each
a group is imagined to be replaced by a
further group, d, the two enantiomers of
a chiral compound, Cabcd, are obtained
(see below).
b
C
a
a
′′
c
b
C
d
a
c
b
C
a
d
c
b
C
a
a
′′
c
Achiral, Caabc
Enantiomers
Achiral, Caabc
Fig. 18
Methylmalonyl-CoA
epimerase. The chiral centers in
the CoA unit do not undergo
inversion during the
epimerization.
COOH
C
H
CH
3
CO-S-CoA
(
S
)
COOH
C
CH
3
H
CO-S-CoA
(
R
)
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