birds have revealed considerable differences in
the kinetic properties, apparently as the result of
adaption to specific functional requirements. For
example, the Michaelis constants vary between
20 and 440 Ilmol/l for aspartic acid, and 12 to
171 Ilmol/l for IMP. Metabolic balance sheets
have been constructed for the various purine
bases and nucleosides of Drosophila melanogaster larvae. Adenosine is converted to inosine
(57%) and AMP (43%), and guanosine to GMP
(92 %); the free base guanine, on the other hand,
is converted to xanthine (84 %) and GMP (only
16 % ); IMP is converted to AMP (65 % ), XMP
and further products (26 % ), and inosine (only
10%).
The production of the nucleoside diphosphates
and triphosphates with their energy-rich bonds
comes about by interaction of the processes of
substrate chain phosphorylation and oxidative
phosphorylation with numerous enzymatic transphosphorylations. Adenylate and guanylate kinases are apparently present in all mammals as
isoenzymes that are encoded at different loci. The
adenylate kinase of muscle (myokinase) catalyses
the reaction 2ADP :=; ATP + AMP. In this way, it
not only provides additional ATP but, in particular, increases the AMP concentration in working
muscle, thereby activating phosphofructokinase
and eventually glycolysis. The myokinase of the
cephalopod Loligo pealeii is inhibited by NADH;
thus, reduction of NADH in working muscle
results in the activation of the enzyme.
Some unusual features of purine metabolism
are found in the brine shrimp Artemia salina,
which is unable to synthesize purines de novo. In
unfavourable conditions, shrimp embryos in the
gastrula stage can withdraw from development by
forming dehydrated cysts. These contain only
2-5 % cell fluid and can survive for several years
without significant metabolism; upon rehydration, they can continue their development to
form nauplius larvae. Protein synthesis resumes
after 10 min, and is quickly followed by RNA synthesis. The purine reserves of the cysts exist
mainly in the form of diguanosine tetraphosphate
(Gp4G); in addition, compounds such as Gp3G,
GpzG, Gp4A and Ap~ are found. The Gp4G
is produced from GTP by a GTP:GTPguanyltransferase, and the Ap~ is formed from
aminoacyl-AMP and ATP by aminoacyl-tRNAsynthetase [39]. The formation of AMP from
Gp4G involves the enzymes dinucleoside tetraphosphatase, GMP reductase, adenylosuccinate
synthase and adenylosuccinate lyase. The enzymes IMP dehydrogenase and GMP synthase are
12.11.2 Adenylate and Guanylate Cyc1ases
449
needed for the conversion of the IMP to GMP.
Some of these enzymes have been isolated and
characterized in detail [39]. The Ap4A produced
in the oocytes of Xenopus laevis by the action of
various aminoacyl-tRNA-synthetases is bound to
a specific protein and has signal functions in DNA
synthesis and cell division [281]. Production of
Ap4A is also catalysed by the luciferase of the
firefly Photinus pyralis [96].
12.11.2 Adenylate and Guanylate Cyclases
These two cyclases catalyse the conversion of
ATP or GTP to the cyclic 3' , 5'-nucleoside monophosphates cAMP and cGMP, which play an
important role as secondary messengers in the
transduction of extracellular signals into the cell.
Adenylate cyclases stimulated by biogenic amines, peptide hormones, protein hormones or
prostaglandins are present in probably all animal
cells. Signal transduction between the corresponding specific receptor and the adenylate cyclase is achieved by the G-proteins (p.309). Several receptor complexes may compete in the cell
membrane for the same adenylate cyclase (floating receptor model). The substrate of the cyclase
is a complex of ATP and a divalent metal ion,
with Mnz+ being more effective than Mg2+. Most
animal adenylate cyclases are activated by fluoride ions.
As well as in the mammals, adenylate cyclases
have been found in insects, crustaceans, xiphosurans, platyhelminths, ciliates and Kinetoplastida,
and are apparently universally distributed. Several hormone-dependent adenylate cyclases from
insects have been functionally characterized but
rarely investigated biochemically. The centralnervous system of various insect species contains
octopamine-dependent adenylate cyclase, which
probably corresponds to the catecholaminedependent enzyme of mammalian brain, but has
a tenfold higher affinity for octopamine than for
noradrenalin or tyramine. However, insect nervous systems additionally contain specific
dopamine- and serotonin-dependent adenylate
cyclases. Octopamine-dependent adenylate cyclases are also present in insect fat bodies, where
they probably play the same role in glycogen
metabolism as does the adrenalin-dependent
enzyme of the mammalian liver [87, 272].
The genetic analysis of Drosophila melanogaster showed that in addition to enzymes linked to
G-proteins or monoamine-receptor-G-protein
complexes, there are also Ca2+ -calmodulin-
the kinetic properties, apparently as the result of
adaption to specific functional requirements. For
example, the Michaelis constants vary between
20 and 440 Ilmol/l for aspartic acid, and 12 to
171 Ilmol/l for IMP. Metabolic balance sheets
have been constructed for the various purine
bases and nucleosides of Drosophila melanogaster larvae. Adenosine is converted to inosine
(57%) and AMP (43%), and guanosine to GMP
(92 %); the free base guanine, on the other hand,
is converted to xanthine (84 %) and GMP (only
16 % ); IMP is converted to AMP (65 % ), XMP
and further products (26 % ), and inosine (only
10%).
The production of the nucleoside diphosphates
and triphosphates with their energy-rich bonds
comes about by interaction of the processes of
substrate chain phosphorylation and oxidative
phosphorylation with numerous enzymatic transphosphorylations. Adenylate and guanylate kinases are apparently present in all mammals as
isoenzymes that are encoded at different loci. The
adenylate kinase of muscle (myokinase) catalyses
the reaction 2ADP :=; ATP + AMP. In this way, it
not only provides additional ATP but, in particular, increases the AMP concentration in working
muscle, thereby activating phosphofructokinase
and eventually glycolysis. The myokinase of the
cephalopod Loligo pealeii is inhibited by NADH;
thus, reduction of NADH in working muscle
results in the activation of the enzyme.
Some unusual features of purine metabolism
are found in the brine shrimp Artemia salina,
which is unable to synthesize purines de novo. In
unfavourable conditions, shrimp embryos in the
gastrula stage can withdraw from development by
forming dehydrated cysts. These contain only
2-5 % cell fluid and can survive for several years
without significant metabolism; upon rehydration, they can continue their development to
form nauplius larvae. Protein synthesis resumes
after 10 min, and is quickly followed by RNA synthesis. The purine reserves of the cysts exist
mainly in the form of diguanosine tetraphosphate
(Gp4G); in addition, compounds such as Gp3G,
GpzG, Gp4A and Ap~ are found. The Gp4G
is produced from GTP by a GTP:GTPguanyltransferase, and the Ap~ is formed from
aminoacyl-AMP and ATP by aminoacyl-tRNAsynthetase [39]. The formation of AMP from
Gp4G involves the enzymes dinucleoside tetraphosphatase, GMP reductase, adenylosuccinate
synthase and adenylosuccinate lyase. The enzymes IMP dehydrogenase and GMP synthase are
12.11.2 Adenylate and Guanylate Cyc1ases
449
needed for the conversion of the IMP to GMP.
Some of these enzymes have been isolated and
characterized in detail [39]. The Ap4A produced
in the oocytes of Xenopus laevis by the action of
various aminoacyl-tRNA-synthetases is bound to
a specific protein and has signal functions in DNA
synthesis and cell division [281]. Production of
Ap4A is also catalysed by the luciferase of the
firefly Photinus pyralis [96].
12.11.2 Adenylate and Guanylate Cyclases
These two cyclases catalyse the conversion of
ATP or GTP to the cyclic 3' , 5'-nucleoside monophosphates cAMP and cGMP, which play an
important role as secondary messengers in the
transduction of extracellular signals into the cell.
Adenylate cyclases stimulated by biogenic amines, peptide hormones, protein hormones or
prostaglandins are present in probably all animal
cells. Signal transduction between the corresponding specific receptor and the adenylate cyclase is achieved by the G-proteins (p.309). Several receptor complexes may compete in the cell
membrane for the same adenylate cyclase (floating receptor model). The substrate of the cyclase
is a complex of ATP and a divalent metal ion,
with Mnz+ being more effective than Mg2+. Most
animal adenylate cyclases are activated by fluoride ions.
As well as in the mammals, adenylate cyclases
have been found in insects, crustaceans, xiphosurans, platyhelminths, ciliates and Kinetoplastida,
and are apparently universally distributed. Several hormone-dependent adenylate cyclases from
insects have been functionally characterized but
rarely investigated biochemically. The centralnervous system of various insect species contains
octopamine-dependent adenylate cyclase, which
probably corresponds to the catecholaminedependent enzyme of mammalian brain, but has
a tenfold higher affinity for octopamine than for
noradrenalin or tyramine. However, insect nervous systems additionally contain specific
dopamine- and serotonin-dependent adenylate
cyclases. Octopamine-dependent adenylate cyclases are also present in insect fat bodies, where
they probably play the same role in glycogen
metabolism as does the adrenalin-dependent
enzyme of the mammalian liver [87, 272].
The genetic analysis of Drosophila melanogaster showed that in addition to enzymes linked to
G-proteins or monoamine-receptor-G-protein
complexes, there are also Ca2+ -calmodulin-