nosoma GDH, which is very unstable and was
at first overlooked, is NAD-specific and is inhibited by ATP and GTP as well as by ADP and
AMP.
12.4.4 Glutamine Synthetases
and Glutaminases
Glutamine is an important product of ammonia
detoxification; it is the storage and transport form
of ammonia, as well as an amino-N donor for
many biosynthetic processes. Glutamine synthetase catalyses the formation of glutamine from
glutamic acid and ammonia with the consumption
of ATP. The cytoplasmic enzyme from the liver,
kidney and brain of mammals and birds consists
of eight identical subunits of about 360-370
amino acids. The isoenzymes from rat liver and
kidney are very different in sequence [193, 229].
Mammalian liver contains a further ammoniadetoxifying enzyme in addition to glutamine synthetase, namely, carbamylphosphate synthetase I. However, the two enzymes are not found in
the same liver cells; glutamine synthetase is
restricted to the hepatocytes in a small region
around the terminal venules, and these contain
no carbamylphosphate synthetase. This alternative expression of two enzymes is apparently
something unique to the mammals; glutamine
synthetase is not restricted to specific liver cells in
other vertebrates [228, 256]. The glutamine synthetase in the liver of uricotelic reptiles and birds
is found in the mitochondria, but releases its
products into the cytoplasm where uric acid synthesis occurs [8, 38]. Mitochondrial glutamine
synthetase are also found in the tortoise, the liver
of which produces both urea and uric acid [37].
The glutamine synthetase in the liver and kidney
of purely ureotelic elasmobranchs is also mitochondrial. In contrast to the situation in reptiles
and birds, the glutamine formed in the liver mitochondria is not released into the cytoplasm but is
further metabolized in situ by the available mitochondrial glutamine-dependent carbamylphosphate synthetase (CPS III). The other organs of
the elasmobranchs contain a cytoplasmic glutamine synthetase which is encoded by the same
gene as that for the mitochondrial enzyme [8].
Drosophila melanogaster also possesses both a
mitochondrial (430 amino acids) and a cytoplasmic (355 amino acids) glutamine synthetase;
in this case, these are encoded by different genes
and show only about 60 % sequence agreement
[35]. The hydrolysis of glutamine is achieved in
12.4.5 Production of Ammonia
417
insects, as in vertebrates, not only by the hydrolytic action of mitochondrial glutaminase I but
also by the system known as "glutaminase II",
which consists of glutamine aminotransferase and
2-oxoglutarate amidase [67].
12.4.5 Production of Ammonia
Various enzymes are involved in ammonia formation in ammoniotelic animals: amino acid oxidases, glutamate dehydrogenases, serine dehydrases, glutaminases, asparaginases, ureases, AMP
deaminases and adenosine deaminases. Little is
known comparatively about the relative contributions of these enzymes. In the bony fish, the gills
are much more important than the kidneys as a
site of ammonia release. However, only a minor
part of the ammonia released is produced in gill
cells, most comes from the blood. Contrary to
early assumptions, glutamine has no role in the
delivery of ammonia to the gills. For example, in
the rainbow trout Salmo gairdneri, the glutamine
concentration in the blood before and after the
gills is about the same (59 versus 57 f,tmolll); in
contrast, both glutamic acid and ammonia concentrations are lowered (28 versus 17 f,tmolll and
230 versus 100 f,tmolll, respectively). The ammonia in the blood comes partly from the liver and
kidneys, which contain high activities of glutamate dehydrogenase and glutaminase, and partly
from active muscles, in which, e.g. in the goldfish, the purine nucleotide cycle and glutamate
dehydrogenase contribute equally to ammonia
production [47, 253].
In the marine crustaceans Praunus flexuosus
and Crangon crangon, ammoniogenesis is due
solely to the activity of glutamate dehydrogenase
[20]. In the earthworm Lumbricus terrestris, the
crayfish Cherax destructor and the estuarine mussel Corbicula japonica, L-serine is the preferred
substrate for ammoniogenesis. In Lumbricus,
however, AMP deaminase and L-serine dehydrase
are involved in ammonia production [105]. In the
corals, brachiopods, molluscs and echinoderms,
the ammonia released in the skeleton-forming tissues is involved in the deposition of calcium carbonate by helping to maintain the optimal pH of
8.6-8.9. In many of these animals, ammoniogenesis depends upon the activity of a very active
urease, which simultaneously produces carbon
dioxide; in the shell-bearing pulmonate snails,
the adenosine deaminase of the mantle tissue is
often more important. This enzyme is also present in non-shelled animals but does not
at first overlooked, is NAD-specific and is inhibited by ATP and GTP as well as by ADP and
AMP.
12.4.4 Glutamine Synthetases
and Glutaminases
Glutamine is an important product of ammonia
detoxification; it is the storage and transport form
of ammonia, as well as an amino-N donor for
many biosynthetic processes. Glutamine synthetase catalyses the formation of glutamine from
glutamic acid and ammonia with the consumption
of ATP. The cytoplasmic enzyme from the liver,
kidney and brain of mammals and birds consists
of eight identical subunits of about 360-370
amino acids. The isoenzymes from rat liver and
kidney are very different in sequence [193, 229].
Mammalian liver contains a further ammoniadetoxifying enzyme in addition to glutamine synthetase, namely, carbamylphosphate synthetase I. However, the two enzymes are not found in
the same liver cells; glutamine synthetase is
restricted to the hepatocytes in a small region
around the terminal venules, and these contain
no carbamylphosphate synthetase. This alternative expression of two enzymes is apparently
something unique to the mammals; glutamine
synthetase is not restricted to specific liver cells in
other vertebrates [228, 256]. The glutamine synthetase in the liver of uricotelic reptiles and birds
is found in the mitochondria, but releases its
products into the cytoplasm where uric acid synthesis occurs [8, 38]. Mitochondrial glutamine
synthetase are also found in the tortoise, the liver
of which produces both urea and uric acid [37].
The glutamine synthetase in the liver and kidney
of purely ureotelic elasmobranchs is also mitochondrial. In contrast to the situation in reptiles
and birds, the glutamine formed in the liver mitochondria is not released into the cytoplasm but is
further metabolized in situ by the available mitochondrial glutamine-dependent carbamylphosphate synthetase (CPS III). The other organs of
the elasmobranchs contain a cytoplasmic glutamine synthetase which is encoded by the same
gene as that for the mitochondrial enzyme [8].
Drosophila melanogaster also possesses both a
mitochondrial (430 amino acids) and a cytoplasmic (355 amino acids) glutamine synthetase;
in this case, these are encoded by different genes
and show only about 60 % sequence agreement
[35]. The hydrolysis of glutamine is achieved in
12.4.5 Production of Ammonia
417
insects, as in vertebrates, not only by the hydrolytic action of mitochondrial glutaminase I but
also by the system known as "glutaminase II",
which consists of glutamine aminotransferase and
2-oxoglutarate amidase [67].
12.4.5 Production of Ammonia
Various enzymes are involved in ammonia formation in ammoniotelic animals: amino acid oxidases, glutamate dehydrogenases, serine dehydrases, glutaminases, asparaginases, ureases, AMP
deaminases and adenosine deaminases. Little is
known comparatively about the relative contributions of these enzymes. In the bony fish, the gills
are much more important than the kidneys as a
site of ammonia release. However, only a minor
part of the ammonia released is produced in gill
cells, most comes from the blood. Contrary to
early assumptions, glutamine has no role in the
delivery of ammonia to the gills. For example, in
the rainbow trout Salmo gairdneri, the glutamine
concentration in the blood before and after the
gills is about the same (59 versus 57 f,tmolll); in
contrast, both glutamic acid and ammonia concentrations are lowered (28 versus 17 f,tmolll and
230 versus 100 f,tmolll, respectively). The ammonia in the blood comes partly from the liver and
kidneys, which contain high activities of glutamate dehydrogenase and glutaminase, and partly
from active muscles, in which, e.g. in the goldfish, the purine nucleotide cycle and glutamate
dehydrogenase contribute equally to ammonia
production [47, 253].
In the marine crustaceans Praunus flexuosus
and Crangon crangon, ammoniogenesis is due
solely to the activity of glutamate dehydrogenase
[20]. In the earthworm Lumbricus terrestris, the
crayfish Cherax destructor and the estuarine mussel Corbicula japonica, L-serine is the preferred
substrate for ammoniogenesis. In Lumbricus,
however, AMP deaminase and L-serine dehydrase
are involved in ammonia production [105]. In the
corals, brachiopods, molluscs and echinoderms,
the ammonia released in the skeleton-forming tissues is involved in the deposition of calcium carbonate by helping to maintain the optimal pH of
8.6-8.9. In many of these animals, ammoniogenesis depends upon the activity of a very active
urease, which simultaneously produces carbon
dioxide; in the shell-bearing pulmonate snails,
the adenosine deaminase of the mantle tissue is
often more important. This enzyme is also present in non-shelled animals but does not