liver-cell receptors initiates the chain of activation
of adenylate cyclase, increase in the level of intracellular cAMP, activation of protein kinase, phosphorylation and, thereby, activation of phosphorylase b kinase, phosphorylation and activation
of the glycogen phosphorylase. At the same time,
glycogen synthesis is inactivated by the cAMPactivated protein kinase; amongst other effects,
this results in an increase in the blood sugar level.
The very rapid activation of glycolysis in active
muscle is due to the fact that the increase in sarcoplasmic calcium concentration, triggered by the
nerve impulse, not only stimulates muscle contraction but also activates the phosphorylase b
kinase. Even the non-phosphorylated enzyme
can be activated by binding of Ca 2 + to the calmodulin subunit; the calcium sensitivity is further
increased by phosphorylation.
Modification by phosphorylation and dephosphorylation appears to be a common mechanism
in the animal phosphorylases. Phosphorylases
and phosphorylase kinases of quite different origin can be freely combined, e.g. the kinase from
rabbit muscle can combine with the phosphorylase of the agnathan Entosphenus japonicus
[286], and even the phosphorylase b of rabbit
muscle can combine with the kinase from Bombyx mori fat bodies. Fat-body extracts from the
lepidopterans Hyalophora cecropia or Manduca
sexta dephosphorylate rabbit phosphorylase a
[233]. The phosphorylase of Drosophila melanogaster is phosphorylated and dephosphorylated
in vitro, not only by the species' own enzymes
but also by those of rabbit muscle [46]. On the
other hand, the different systems of the phosphorylation/dephosphorylation of glycogen phosphorylase show considerable species-specific differences. For example, the phosphorylase b
kinase from the muscle of the spiny dogfish SquaIus acanthias shows greater specificity than does
that of the rabbit; this enzyme cannot utilize
GTP as the phosphate donor nor can it phosphorylate troponin. The Squalus enzyme is absolutely calcium dependent but is neither phosphorylated nor dephosphorylated; it is not clear
whether it is hormonally regulated [194]. The
idea that the conversion of the b form to the a
form is central to the regulation of animal glycogen phosphorylases has been brought into question by investigations of the lugworm Arenicola
marina. Normally one-third of the enzyme is
found as the a form; anoxia has no effect on the
proportion of the a form or on the total phosphorylase activity. The isolated b form is phosphorylated only 40 % by the rabbit-muscle phosphory14.2 Glycogen Phosphorylases
521
lase kinase. The increase in the rate of glycolysis
during anoxia is apparently not related to phosphorylation of the b form but to the AMP activation of the a form present [115].
The insect phosphorylases are stimulated by
octopamine and by adipokinetic or hyperglycaemic neuropeptides (AKHs). There is some
suggestion that cAMP-dependent protein kinase
and phosphorylase b kinase are involved in this
hormonal regulation in a way that is similar to
that in higher vertebrates, but there is no direct
evidence for this. Hormone-induced increases in
the cAMP level and activation of the phosphorylase by cAMP have already been demonstrated in
several insect species, but it is still possible that
cAMP functions indirectly via stimulation of calcium uptake into the cells [46, 233]. In the cockroach Periplaneta americana, the conversion of
phosphorylase b into the a form, brought about
by the hyperglycaemic peptide hormone, is not
accompanied by an increase in the cAMP level
[182].
Cold activates the fat-body phosphorylase in
many insects; as a result, the glycogen stored in
the fat body is hydrolysed and large amounts of
trehalose or polyvalent alcohols, such as glycerol
and/or sorbitol, are produced and accumulated.
For example, in the diapause pupae of the silkworm Hyalophora cecropia the glycerol concentration in the haemolymph increases within
30 days at 4 °C from 250 mmolll to over
600 mmolll; coincident with the decrease in temperature, the proportion of phosphorylase a
increases within 1 h from about 10 to more than
50 %. This also occurs in isolated fat bodies and
can be explained by the fact that at temperatures
of around 0 °C the phosphorylase kinase is still
weakly active but the phosphatase is completely
inactive [33, 95,233]. Cold activation of glycogen
phosphorylase has also been found in the liver of
the terrestrial hibernating frog Rana sylvatica.
This amphibian survives freezing of its extracellular fluids because its tissues are protected by glucose concentrations of over 200 !!mol/g wet
weight [42].
The in vitro phosphorylation of phosphorylase
b may result in a partially phosphorylated alb
form with intermediate catalytic properties. In
some animals, three variously phosphorylated
phosphorylase forms have also been found in living cells, e.g. in the insects Locusta migratoria
and Periplaneta americana, in the lobster, in the
scallop Pecten maximus, and even in the muscles
of the crucian carp Carassius carassius [73, 150,
223].
of adenylate cyclase, increase in the level of intracellular cAMP, activation of protein kinase, phosphorylation and, thereby, activation of phosphorylase b kinase, phosphorylation and activation
of the glycogen phosphorylase. At the same time,
glycogen synthesis is inactivated by the cAMPactivated protein kinase; amongst other effects,
this results in an increase in the blood sugar level.
The very rapid activation of glycolysis in active
muscle is due to the fact that the increase in sarcoplasmic calcium concentration, triggered by the
nerve impulse, not only stimulates muscle contraction but also activates the phosphorylase b
kinase. Even the non-phosphorylated enzyme
can be activated by binding of Ca 2 + to the calmodulin subunit; the calcium sensitivity is further
increased by phosphorylation.
Modification by phosphorylation and dephosphorylation appears to be a common mechanism
in the animal phosphorylases. Phosphorylases
and phosphorylase kinases of quite different origin can be freely combined, e.g. the kinase from
rabbit muscle can combine with the phosphorylase of the agnathan Entosphenus japonicus
[286], and even the phosphorylase b of rabbit
muscle can combine with the kinase from Bombyx mori fat bodies. Fat-body extracts from the
lepidopterans Hyalophora cecropia or Manduca
sexta dephosphorylate rabbit phosphorylase a
[233]. The phosphorylase of Drosophila melanogaster is phosphorylated and dephosphorylated
in vitro, not only by the species' own enzymes
but also by those of rabbit muscle [46]. On the
other hand, the different systems of the phosphorylation/dephosphorylation of glycogen phosphorylase show considerable species-specific differences. For example, the phosphorylase b
kinase from the muscle of the spiny dogfish SquaIus acanthias shows greater specificity than does
that of the rabbit; this enzyme cannot utilize
GTP as the phosphate donor nor can it phosphorylate troponin. The Squalus enzyme is absolutely calcium dependent but is neither phosphorylated nor dephosphorylated; it is not clear
whether it is hormonally regulated [194]. The
idea that the conversion of the b form to the a
form is central to the regulation of animal glycogen phosphorylases has been brought into question by investigations of the lugworm Arenicola
marina. Normally one-third of the enzyme is
found as the a form; anoxia has no effect on the
proportion of the a form or on the total phosphorylase activity. The isolated b form is phosphorylated only 40 % by the rabbit-muscle phosphory14.2 Glycogen Phosphorylases
521
lase kinase. The increase in the rate of glycolysis
during anoxia is apparently not related to phosphorylation of the b form but to the AMP activation of the a form present [115].
The insect phosphorylases are stimulated by
octopamine and by adipokinetic or hyperglycaemic neuropeptides (AKHs). There is some
suggestion that cAMP-dependent protein kinase
and phosphorylase b kinase are involved in this
hormonal regulation in a way that is similar to
that in higher vertebrates, but there is no direct
evidence for this. Hormone-induced increases in
the cAMP level and activation of the phosphorylase by cAMP have already been demonstrated in
several insect species, but it is still possible that
cAMP functions indirectly via stimulation of calcium uptake into the cells [46, 233]. In the cockroach Periplaneta americana, the conversion of
phosphorylase b into the a form, brought about
by the hyperglycaemic peptide hormone, is not
accompanied by an increase in the cAMP level
[182].
Cold activates the fat-body phosphorylase in
many insects; as a result, the glycogen stored in
the fat body is hydrolysed and large amounts of
trehalose or polyvalent alcohols, such as glycerol
and/or sorbitol, are produced and accumulated.
For example, in the diapause pupae of the silkworm Hyalophora cecropia the glycerol concentration in the haemolymph increases within
30 days at 4 °C from 250 mmolll to over
600 mmolll; coincident with the decrease in temperature, the proportion of phosphorylase a
increases within 1 h from about 10 to more than
50 %. This also occurs in isolated fat bodies and
can be explained by the fact that at temperatures
of around 0 °C the phosphorylase kinase is still
weakly active but the phosphatase is completely
inactive [33, 95,233]. Cold activation of glycogen
phosphorylase has also been found in the liver of
the terrestrial hibernating frog Rana sylvatica.
This amphibian survives freezing of its extracellular fluids because its tissues are protected by glucose concentrations of over 200 !!mol/g wet
weight [42].
The in vitro phosphorylation of phosphorylase
b may result in a partially phosphorylated alb
form with intermediate catalytic properties. In
some animals, three variously phosphorylated
phosphorylase forms have also been found in living cells, e.g. in the insects Locusta migratoria
and Periplaneta americana, in the lobster, in the
scallop Pecten maximus, and even in the muscles
of the crucian carp Carassius carassius [73, 150,
223].