424
12 Small Nitrogenous Compounds
mals or invertebrates. In the cephalopod Loligo
pealei, the sulphur from labelled cysteine is incorporated into isethionic acid but the carbon atoms
are not [112].
12.5.3 Serine
The degradation of L-serine can occur by two routes. L-serine is either converted directly to pyruvate by the action of L-serine dehydratase (SOH),
or hydroxypyruvate is produced by L-serine:
pyruvate aminotransferase (SPAT) and then
introduced into glycolysis via D-glycerate and 2phosphoglycerate [231]. The relative activities of
these two pathways in vertebrates vary with the
species and the organ involved. SOH activity in
mammals is confined to the liver; it is present at a
low level in the liver of the turtle Testudo graeca
but is lacking in Emys europaea, various amphibians and the goldfish. The sequence of mammalian
SOH has some similarities to microbial threonine
dehydratase, and this suggests a common origin.
Compared with human SOH (328 amino acids),
the homologous rat enzyme is extended by an
insertion of 36 amino acids between positions 64
and 65 [170]. SPAT is found in mammalian kidney and in the liver. The liver of carnivorous
mammals has a consistently higher activity
(1600-4200 mU/g) than that of omnivorous or
herbivorous animals (always less than 390 mU/g).
The activity in the carnivorous turtle Emys is
180 mU/g, in the herbivorous Testudo only
50 mU/g, and in various amphibians and the
goldfish about 800 mU/g. The SPAT activity of
the kidneys is also correlated to the feeding habit.
The mitochondria and the peroxisomes of rat
liver contain different SPATh, the mRNAs of
which arise from the same gene by alternative
splicing [169].
12.5.4 'ftyptophan
This amino acid has the most complicated spectrum of metabolism (Fig. 12.9). In mammals, the
main pathway concerns the oxidative opening of
the ring of 3-hydroxyanthranilic acid to give the
unstable 2-amino-3-carboxy-muconic acid semialdehyde, and from this compound, on the one
hand, to yield acetoacetyl-CoA and CO2 and, on
the other hand, to give nicotinamide. Other
metabolites, e.g. 5-hydroxyindole acetic acid, are
found only in trace amounts, and part of this
represents metabolism by gut bacteria. Insects
are not able to cleave the benzene ring of 3hydroxyanthranilic acid and completely degrade
tryptophan to CO2, This is shown by the accumulation of intermediates that occur before the
cleavage reaction, the fact that radioactive CO2 is
not produced from 14C-tryptophan labelled in the
benzene ring and, in contrast to mammals, the
absence of any sparing effect on nicotinic acid by
tryptophan in the diet. In the insects, tryptophan
metabolism from 3-hydroxykynurenine leads
mainly to ommochromes, a group of brown, red
or violet pigments which occur in the eye and epidermis, and also are found in the excrement
(p.748). We can only speculate about the evolutionary significance of this fundamental difference in tryptophan metabolism between insects
and mammals. nyptophan is in fact one of the
rarer of the 20 protein amino acids, making up
less than 1 mol %; an excess disturbs development and can be carcinogenic. It is feasible that
ommochrome synthesis is primarily a mechanism
for detoxifying tryptophan, and has evolved in
those animals that have lost the ability to completely degrade tryptophan [137].
Over and above comparative biochemistry,
great interest in the biosynthesis of ommochrome
has developed owing to the existence of enzymedeficient mutants with which the mechanisms of
gene action can be studied. The investigations of
KUhn on the flour moth Ephestia and those of
Beadle and Ephrussi on Drosophila are among
the fundamental studies which, at the beginning
of the 1930s, led to the formulation of the "one
gene - one enzyme" hypothesis. Thus, the tryptophan metabolism of the insects has been relatively thoroughly studied, but otherwise there is
very little in the way of comparative biochemistry.
The formation of 3-hydroxyanthranilic acid has
been observed in tracer studies with all animals
examined, but oxidative degradation of the benzene ring is found only in vertebrates of all
classes, the snail OtaZa sp., and the oligochaete
Eudrilus engineae; it does not occur in the crayfish Cambarus virilis and the insects. However,
the first three enzymes of oxidative degradation
(3-hydroxyanthranilic acid-3,4-dioxygenase, 2amino-3-carboxymuconic acid semialdehyde decarboxylase and 2-aminomuconic acid semialdehyde dehydrogenase) have been detected in the
liver and kidneys only of vertebrates and not in
the invertebrates, although one must presume
their existence in OtaZa and Eudrilus. As well as
in various arthropods, ommochrome is found in
cnidarians, polychaetes, echiurida and cephalopods.
12 Small Nitrogenous Compounds
mals or invertebrates. In the cephalopod Loligo
pealei, the sulphur from labelled cysteine is incorporated into isethionic acid but the carbon atoms
are not [112].
12.5.3 Serine
The degradation of L-serine can occur by two routes. L-serine is either converted directly to pyruvate by the action of L-serine dehydratase (SOH),
or hydroxypyruvate is produced by L-serine:
pyruvate aminotransferase (SPAT) and then
introduced into glycolysis via D-glycerate and 2phosphoglycerate [231]. The relative activities of
these two pathways in vertebrates vary with the
species and the organ involved. SOH activity in
mammals is confined to the liver; it is present at a
low level in the liver of the turtle Testudo graeca
but is lacking in Emys europaea, various amphibians and the goldfish. The sequence of mammalian
SOH has some similarities to microbial threonine
dehydratase, and this suggests a common origin.
Compared with human SOH (328 amino acids),
the homologous rat enzyme is extended by an
insertion of 36 amino acids between positions 64
and 65 [170]. SPAT is found in mammalian kidney and in the liver. The liver of carnivorous
mammals has a consistently higher activity
(1600-4200 mU/g) than that of omnivorous or
herbivorous animals (always less than 390 mU/g).
The activity in the carnivorous turtle Emys is
180 mU/g, in the herbivorous Testudo only
50 mU/g, and in various amphibians and the
goldfish about 800 mU/g. The SPAT activity of
the kidneys is also correlated to the feeding habit.
The mitochondria and the peroxisomes of rat
liver contain different SPATh, the mRNAs of
which arise from the same gene by alternative
splicing [169].
12.5.4 'ftyptophan
This amino acid has the most complicated spectrum of metabolism (Fig. 12.9). In mammals, the
main pathway concerns the oxidative opening of
the ring of 3-hydroxyanthranilic acid to give the
unstable 2-amino-3-carboxy-muconic acid semialdehyde, and from this compound, on the one
hand, to yield acetoacetyl-CoA and CO2 and, on
the other hand, to give nicotinamide. Other
metabolites, e.g. 5-hydroxyindole acetic acid, are
found only in trace amounts, and part of this
represents metabolism by gut bacteria. Insects
are not able to cleave the benzene ring of 3hydroxyanthranilic acid and completely degrade
tryptophan to CO2, This is shown by the accumulation of intermediates that occur before the
cleavage reaction, the fact that radioactive CO2 is
not produced from 14C-tryptophan labelled in the
benzene ring and, in contrast to mammals, the
absence of any sparing effect on nicotinic acid by
tryptophan in the diet. In the insects, tryptophan
metabolism from 3-hydroxykynurenine leads
mainly to ommochromes, a group of brown, red
or violet pigments which occur in the eye and epidermis, and also are found in the excrement
(p.748). We can only speculate about the evolutionary significance of this fundamental difference in tryptophan metabolism between insects
and mammals. nyptophan is in fact one of the
rarer of the 20 protein amino acids, making up
less than 1 mol %; an excess disturbs development and can be carcinogenic. It is feasible that
ommochrome synthesis is primarily a mechanism
for detoxifying tryptophan, and has evolved in
those animals that have lost the ability to completely degrade tryptophan [137].
Over and above comparative biochemistry,
great interest in the biosynthesis of ommochrome
has developed owing to the existence of enzymedeficient mutants with which the mechanisms of
gene action can be studied. The investigations of
KUhn on the flour moth Ephestia and those of
Beadle and Ephrussi on Drosophila are among
the fundamental studies which, at the beginning
of the 1930s, led to the formulation of the "one
gene - one enzyme" hypothesis. Thus, the tryptophan metabolism of the insects has been relatively thoroughly studied, but otherwise there is
very little in the way of comparative biochemistry.
The formation of 3-hydroxyanthranilic acid has
been observed in tracer studies with all animals
examined, but oxidative degradation of the benzene ring is found only in vertebrates of all
classes, the snail OtaZa sp., and the oligochaete
Eudrilus engineae; it does not occur in the crayfish Cambarus virilis and the insects. However,
the first three enzymes of oxidative degradation
(3-hydroxyanthranilic acid-3,4-dioxygenase, 2amino-3-carboxymuconic acid semialdehyde decarboxylase and 2-aminomuconic acid semialdehyde dehydrogenase) have been detected in the
liver and kidneys only of vertebrates and not in
the invertebrates, although one must presume
their existence in OtaZa and Eudrilus. As well as
in various arthropods, ommochrome is found in
cnidarians, polychaetes, echiurida and cephalopods.