Chirality in Biology
589
rat nervous tissues and endocrine glands
increase following administration of
D-
aspartate. Experiments with homogenates
haveshownanenzyma
t
i
cme
thy
lg
roup
transfer from
S
-adenosylmethionine to D-
aspartate yielding NMDA. The highest
level of transferase activity was in the
hypothalamus with signiFcant levels in
rat hippocampus, adenohypophysis, brain,
and liver.
D-aspartate and NMDA may influence
hormone release in various cells. In the
case of prolactin (PRL) and the prolactin
releasing factor (PR±), NMDA, synthe-
sized in both brain and hypothalamus,
stimulates the release of PR± in the hy-
pothalamus. In turn, PRL is then released
in the hypophysis. D-aspartate also acts
directly on the adenohypophysis, further
reinforcing PRL release. D-aspartate occurs
at the level of 120 nmol mL
−
1
in testicu-
lar venous blood plasma with lower levels
in other components; the values are all
higher than those for peripheral blood
plasma (6 nmol mL
−
1
). The distribution
of D-aspartate in rat testes is quite dif-
ferent from that of testosterone. The role
of
D-aspartate in the male reproductive
tract remains unclear, although it may
be involved in steroid synthesis in rat
testis.
D-Enantiomers of several amino acids
occur in various species of hyperther-
mophilic
Archaea
(e.g. species of
Desul-
furococcus
,
Pyrococcus
,and
Thermococcus
).
Remarkably, in the case of aspartate,
almost 50% of the total content was the D-
enantiomer (for the ratio, D-aspartate/total
D-
+
L-aspartate, values ranged from 43.0
to 49.1%). SigniFcant levels of racem-
ization were also observed for alanine,
leucine, lysine, and phenylalanine. As-
partate racemase activity was detected in
crude extracts from various strains and an
aspartate racemase gene was cloned and
sequenced from
Thermococcus sp
.s
t
r
a
in
KS-8. Since peptidoglycan – a usual source
of bacterial D-alanine (see below) – is not
present in the
Archaea
, the function of
D-amino acid enantiomers in these organ-
isms is unclear. Several
D-amino acids
occur in insects.
D-Alanine
is present
in hemolymph of milkweed bugs (
On-
copeltus fasciatus
), and free and combined
forms of D-serine occur in silkworms and
earthworms.
D-Amino
acids function in the com-
plex
structures
of
some
bacterial
cell
walls. These peptidoglycans (mureins) are
polysaccharides with alternating units of
N
-acetyl-D-glucosamine and
N
-acetylmur-
amic acid. The latter units are linked
to a tetrapeptide containing at least one
D-amino
acid. In
Staphylococcus aureus
,
the tetrapeptide is
L-ala-D-isoglu-L-lys-D-
ala (in isoglutamate, the peptide bond
is formed with the
γ
-carboxyl group).
In
E. coli
,
meso
-diaminopimelate replaces
L-lysine, and depending on the speciFc
organism, other variations are possible.
The capsular substance of anthrax bacil-
lus (
Bacillus anthracis
),
Bacillus subtilis
,and
other bacteria consists entirely of poly-D-
glutamate.
D-Amino acids also occur in relatively
small peptides and related structures pro-
duced by microorganisms, for example,
penicillin, in
which
the
penicillamine
unit
(
ββ
-dimethylcysteine)
has
the
D-
conFguration. Penicillin has three chiral
centers; two of them derive from a tripep-
tide precursor,
δ
(L-
α
-aminoadipoyl)-L-cys-
D-valine. The gramicidins are antibiotic
bacterial peptides synthesized by a mul-
tienzyme complex rather than by the
ribosomal mechanism. In gramicidin A,
a channel-forming ionophore, the peptide
chain, contains 15 amino acid residues;
with the exception of an achiral glycine
unit, units with D
-and L-conFgurations
