14.7.2 Pyruvate Kinase Isoenzymes
of Other Vertebrates
The pattern of PK isoenzymes from the mammals
to the amphibians is very similar. It is, of course,
questionable whether PK forms from lower vertebrates or even invertebrates can be related to
particular isoenzymes of the mammals solely on
the basis of electrophoretic data; at least their
kinetic-regulatory properties should also be taken
into consideration. The L type is not detected
electrophoretically in the birds or the urodelans,
and although it is recognized immunologically in
the chicken, the avian liver PK does not react
with glucagon or cAMP. In the clawed frog Xenopus laevis, no less than nine PK isoenzymes may
be separated by isoelectric focusing; these have
been identified as L, M2 and Ml homotetramers
and as M2L and MIM2 hybrids. The initial subunits in the embryo are M2 and L, with Ml appearing
later; the PK of oocytes and embryos correspondingly shows sigmoidal PEP kinetics [50]. The socalled L type has a relatively high PEP affinity
and low PEP cooperativity, and it is not affected
by cAMP-dependent phosphorylation; thus, this
PK corresponds more to mammalian PK-M2 than
to PK-L [60].
The situation in the fish is especially complicated. The cartilaginous fish have only the M2
type; in the teleosts there is almost always an
additional E type, with M2E hybrid molecules
occurring quite frequently in the heart. The liver
and erythrocytes of many species contain a third
type "L" which, however, cannot be compared
directly with the PK-L of the mammals [204]. In
complete contrast to the mammals, the skeletal
muscle PKs of many fish have distinct allosteric
characteristics, whereas the liver PK is only
weakly regulated. The regulation of the muscle
PK varies widely with the species. For example,
the muscle PK of two out of four Amazonian fish
species responds strongly to the usual allosteric
effectors, whereas the others respond only
weakly, and this is not related to whether the species respire in water or in air.
The tissue-specific PK isoenzymes of the fish
often show only minor differences in regulatory
characters. Of the two PK isoenzymes in the pink
salmon Oncorhynchus kisutch, the predominant
type found in the muscle and heart is PK-Mb
whereas the form that is more generally distributed is PK-M2; both show allosteric properties,
although PK-M2 appears to be more easily regulated than PK-M1. PK-M2 shows immunological
cross-reactivity not only with PK-M1 of the same
14.7.3 Pyruvate Kinases ofInvertebrates
531
species but also with PK-M1 and PK-L of the
mammals. The muscle enzyme of the sturgeon
Acipenser fulvescens, which shows strong allosteric effects, exhibits immunological crossreactivity with PK-M1 of the frog and the dog
[87]. Thus, the far-reaching differences in kineticregulatory properties appear to be the result of
relatively minor differences in sequence [91]. The
red and white muscles of the American eel
Anguilla rostrata contain different PKs but both
types are regulated allosterically. It is likely that
the red muscles of the migrating eel, in which the
liver degenerates, have gluconeogenic functions.
The liver PKs of A. rostrata and of the rainbow
trout Salmo gairdneri both have no allosteric
properties [206]. On the other hand, the Amazonian fish Arapaima gigas has different PKs in the
liver and kidneys; both can be regulated and
appear to allow gluconeogenesis in both organs.
The liver of the flounder Platichthys flesus has
two PKs, one of which is much more strongly
inhibited by phenylalanine than the other; it is
therefore specifically adapted to gluconeogenic
metabolic conditions [216].
14.7.3 Pyruvate Kinases of Invertebrates
With the exception of several parasitic worms
such as Ascaris lumbricoides, which because of
the peculiarities of its carbohydrate metabolism
has negligible PK activity, all invertebrates have
one or more PKs. Tissue-specific isoenzymes
have been reported, for example, in the mussels
Crassostrea and Mytilus, the sea snail Busycotypus, the cephalopod Octopus, the crayfish Orconectes, and the insects Periplaneta and Schistocerca [36, 63, 192, 245]. Busycotypus canaliculatum has three PK isoenzymes distributed between
red muscle, e.g. of the radula retractor and heart
ventricle, white muscle of the foot and mantle,
and non-muscle tissues such as the gill, kidney
and hepatopancreas [192].
Most of the invertebrate PKs can be allosterically modulated; in some cases, covalent modification by phosphorylation/dephosphorylation has
also been reported. The PKs from tissues with a
high potential for gluconeogenesis are especially
well regulated; examples include the hepatopancreas of various molluscs [29, 158, 215], the hepatopancreas and hypodermis of crustaceans, and
the fat bodies of insects [63, 245]. Most facultative anaerobic muscles of the invertebrates also
contain PKs with complex allosteric properties
[158,246]. In contrast, the PKs of predominantly
of Other Vertebrates
The pattern of PK isoenzymes from the mammals
to the amphibians is very similar. It is, of course,
questionable whether PK forms from lower vertebrates or even invertebrates can be related to
particular isoenzymes of the mammals solely on
the basis of electrophoretic data; at least their
kinetic-regulatory properties should also be taken
into consideration. The L type is not detected
electrophoretically in the birds or the urodelans,
and although it is recognized immunologically in
the chicken, the avian liver PK does not react
with glucagon or cAMP. In the clawed frog Xenopus laevis, no less than nine PK isoenzymes may
be separated by isoelectric focusing; these have
been identified as L, M2 and Ml homotetramers
and as M2L and MIM2 hybrids. The initial subunits in the embryo are M2 and L, with Ml appearing
later; the PK of oocytes and embryos correspondingly shows sigmoidal PEP kinetics [50]. The socalled L type has a relatively high PEP affinity
and low PEP cooperativity, and it is not affected
by cAMP-dependent phosphorylation; thus, this
PK corresponds more to mammalian PK-M2 than
to PK-L [60].
The situation in the fish is especially complicated. The cartilaginous fish have only the M2
type; in the teleosts there is almost always an
additional E type, with M2E hybrid molecules
occurring quite frequently in the heart. The liver
and erythrocytes of many species contain a third
type "L" which, however, cannot be compared
directly with the PK-L of the mammals [204]. In
complete contrast to the mammals, the skeletal
muscle PKs of many fish have distinct allosteric
characteristics, whereas the liver PK is only
weakly regulated. The regulation of the muscle
PK varies widely with the species. For example,
the muscle PK of two out of four Amazonian fish
species responds strongly to the usual allosteric
effectors, whereas the others respond only
weakly, and this is not related to whether the species respire in water or in air.
The tissue-specific PK isoenzymes of the fish
often show only minor differences in regulatory
characters. Of the two PK isoenzymes in the pink
salmon Oncorhynchus kisutch, the predominant
type found in the muscle and heart is PK-Mb
whereas the form that is more generally distributed is PK-M2; both show allosteric properties,
although PK-M2 appears to be more easily regulated than PK-M1. PK-M2 shows immunological
cross-reactivity not only with PK-M1 of the same
14.7.3 Pyruvate Kinases ofInvertebrates
531
species but also with PK-M1 and PK-L of the
mammals. The muscle enzyme of the sturgeon
Acipenser fulvescens, which shows strong allosteric effects, exhibits immunological crossreactivity with PK-M1 of the frog and the dog
[87]. Thus, the far-reaching differences in kineticregulatory properties appear to be the result of
relatively minor differences in sequence [91]. The
red and white muscles of the American eel
Anguilla rostrata contain different PKs but both
types are regulated allosterically. It is likely that
the red muscles of the migrating eel, in which the
liver degenerates, have gluconeogenic functions.
The liver PKs of A. rostrata and of the rainbow
trout Salmo gairdneri both have no allosteric
properties [206]. On the other hand, the Amazonian fish Arapaima gigas has different PKs in the
liver and kidneys; both can be regulated and
appear to allow gluconeogenesis in both organs.
The liver of the flounder Platichthys flesus has
two PKs, one of which is much more strongly
inhibited by phenylalanine than the other; it is
therefore specifically adapted to gluconeogenic
metabolic conditions [216].
14.7.3 Pyruvate Kinases of Invertebrates
With the exception of several parasitic worms
such as Ascaris lumbricoides, which because of
the peculiarities of its carbohydrate metabolism
has negligible PK activity, all invertebrates have
one or more PKs. Tissue-specific isoenzymes
have been reported, for example, in the mussels
Crassostrea and Mytilus, the sea snail Busycotypus, the cephalopod Octopus, the crayfish Orconectes, and the insects Periplaneta and Schistocerca [36, 63, 192, 245]. Busycotypus canaliculatum has three PK isoenzymes distributed between
red muscle, e.g. of the radula retractor and heart
ventricle, white muscle of the foot and mantle,
and non-muscle tissues such as the gill, kidney
and hepatopancreas [192].
Most of the invertebrate PKs can be allosterically modulated; in some cases, covalent modification by phosphorylation/dephosphorylation has
also been reported. The PKs from tissues with a
high potential for gluconeogenesis are especially
well regulated; examples include the hepatopancreas of various molluscs [29, 158, 215], the hepatopancreas and hypodermis of crustaceans, and
the fat bodies of insects [63, 245]. Most facultative anaerobic muscles of the invertebrates also
contain PKs with complex allosteric properties
[158,246]. In contrast, the PKs of predominantly