14.11.2 Lactate Debydrogenases
of Invertebrates
In comparison with the vertebrate enzymes, the
L-specific LDHs of the invertebrates have no special features. They are almost all tetramers of
about 140 kDa [63, 70]. A dimeric L-specific
LDH of 70 kDa has been isolated from a squid
(Loligo vulgaris) which, due to a genetic defect,
had no octopine dehydrogenase in the mantle but
showed high LDH activity [67]. The assumption
that all these enzymes are homologous to vertebrate LDH awaits confirmation by sequence comparisons. In substrate affinity and pyruvate
inhibition, most invertebrate LDHs are intermediate between the muscle and heart types of
the vertebrates [63, 67]. Isoenzymes of L-specific
LDH have been reported for only a few invertebrates. The LDH from the brain of the lobster
Homarus americanus gives a five-banded electrophoretic pattern; a B-like type predominates in
the tail muscle, and an A-like type predominates
in the leg muscle. The crayfish Orconectes limosus, in contrast, has no LDH isoenzymes [70]. In
the cephalopod Sepia officinalis, B-like forms
with marked pyruvate inhibition are found in the
heart, gill, brain, nidamental gland and ovary,
and an A-like form with little substrate inhibition
is found in the mantle muscle, hepatopancreas
and skin [70]. The five-banded pattern found in
the mosquito Aedes aegyti probably arises by random combination of two different subunits, one
of which predominates in the head and the other
in the thorax and abdomen. Two LDHs are present in the tapeworm Hymenolepsis diminuta,
one being expressed in all tissues and the other
only in the ripe ovary and eggs. The small liverfluke Dicrocoelium dendriticum possesses six
LDH isoenzymes and the larger Fasciola hepatica
has four [137]. The allosteric activation by fructose bisphosphate shown by the L-specific LDH
of the turbellarian Polycelis nigra is a peculiarity
which otherwise probably occurs only in some
parasitic platyhelminths.
The first D-specific LDH of the animal kingdom was discovered in 1968 in the xiphosuran
Limulus polyphemus [27]. Since then, many systematic studies have shown that D- or L-specific
enzymes are present in all animal groups. The distribntion of tbe two enzyme types is extraordinarily sporadic (Table 14.6). The conclusions
reached are that L- and D-specific LDHs are
homologous, that few amino acid substitutions
are required to change the stereo-specificity, and
that an LID switch has occurred many times in
14.11.2 Lactate Dehydrogenases oflnvertebrates
545
LDH evolution [144]. However, comparisons of
the tryptic digest patterns of D-specific Limulus
LDH and L-specific vertebrate LDH show such
large differences that only a comparison of the
amino acid sequences will determine whether or
not the two LDH types are homologous [229]. In
any case, D-Iactate can be metabolized in some
circumstances even in animals that possess only Lspecific LDH. Mammalian liver, in fact, can turn
over D-Iactate IS-fold faster than L-Iactate. This is
of particular importance in the ruminants, where
the D-Iactate produced in the rumen by symbiontic bacteria is oxidized with the help of
mitochondrial D-2-bydroxy-acid dehydrogenases,
which are found especially in the brain cortex but
also in the heart and liver [92].
D-Specific LDHs have been isolated from various animals and have been characterized: from
the xiphosuran Limulus polyphemus, the barnacle Balanus nubilis, the polychaete Nereis
virens, the cockle Cardium edule and the snails
Helix pomatia, H. aspersa, Haliotis cracherodii
and Achatina achatina [27,70,261]. The majority
of D-specific LDHs are dimers of 70-80 kDa. The
enzyme from Helix aspersa was described earlier
as a tetramer but, more recently, was described as
a dimer. The D-specific LDHs of the barnacle
Balanus nubilis and the snail Achatina achatina
are, however, tetrameric [261]. In their general
catalytic properties, most of the D-specific invertebrate LDHs lie intermediate between the heart
and muscle types of the vertebrates. Some, e.g.
from Limulus, Haliotis and Achatina, are inhibited by pyruvate but others, e.g. from Cardium
and Helix aspersa, are not [27, 261]. At least the
enzymes from Balanus, Haliotis and Helix
aspersa show relatively high activity against 2keto- and 2-hydroxybutyrate.
Limulus polyphemus has a complicated system
of tissne-specific isoenzymes which must be considered in relation to processing of the end products arising from activity-dependent anaerobiosis.
Altogether, there are four different LDH subunits, A-D, which form six dimeric isoenzymes: a
"heart-type triad" (AA, AB, BB) and a "muscletype triad" (CC, CD, DD). The muscle-type triad
predominates in the skeletal muscles, and the
heart type predominates in the hepatopancreas;
the heart contains more of the muscle-type LDH
than of the heart type. The lactate affinity and the
pyruvate sensitivity decrease in the order AB >
BB > CD > DD. Under physiological conditions, lactate prodl).~tion is clearly preferred by
the muscle type, whereas the predominant heart
type of the hepatopancreas is active in both direc-
of Invertebrates
In comparison with the vertebrate enzymes, the
L-specific LDHs of the invertebrates have no special features. They are almost all tetramers of
about 140 kDa [63, 70]. A dimeric L-specific
LDH of 70 kDa has been isolated from a squid
(Loligo vulgaris) which, due to a genetic defect,
had no octopine dehydrogenase in the mantle but
showed high LDH activity [67]. The assumption
that all these enzymes are homologous to vertebrate LDH awaits confirmation by sequence comparisons. In substrate affinity and pyruvate
inhibition, most invertebrate LDHs are intermediate between the muscle and heart types of
the vertebrates [63, 67]. Isoenzymes of L-specific
LDH have been reported for only a few invertebrates. The LDH from the brain of the lobster
Homarus americanus gives a five-banded electrophoretic pattern; a B-like type predominates in
the tail muscle, and an A-like type predominates
in the leg muscle. The crayfish Orconectes limosus, in contrast, has no LDH isoenzymes [70]. In
the cephalopod Sepia officinalis, B-like forms
with marked pyruvate inhibition are found in the
heart, gill, brain, nidamental gland and ovary,
and an A-like form with little substrate inhibition
is found in the mantle muscle, hepatopancreas
and skin [70]. The five-banded pattern found in
the mosquito Aedes aegyti probably arises by random combination of two different subunits, one
of which predominates in the head and the other
in the thorax and abdomen. Two LDHs are present in the tapeworm Hymenolepsis diminuta,
one being expressed in all tissues and the other
only in the ripe ovary and eggs. The small liverfluke Dicrocoelium dendriticum possesses six
LDH isoenzymes and the larger Fasciola hepatica
has four [137]. The allosteric activation by fructose bisphosphate shown by the L-specific LDH
of the turbellarian Polycelis nigra is a peculiarity
which otherwise probably occurs only in some
parasitic platyhelminths.
The first D-specific LDH of the animal kingdom was discovered in 1968 in the xiphosuran
Limulus polyphemus [27]. Since then, many systematic studies have shown that D- or L-specific
enzymes are present in all animal groups. The distribntion of tbe two enzyme types is extraordinarily sporadic (Table 14.6). The conclusions
reached are that L- and D-specific LDHs are
homologous, that few amino acid substitutions
are required to change the stereo-specificity, and
that an LID switch has occurred many times in
14.11.2 Lactate Dehydrogenases oflnvertebrates
545
LDH evolution [144]. However, comparisons of
the tryptic digest patterns of D-specific Limulus
LDH and L-specific vertebrate LDH show such
large differences that only a comparison of the
amino acid sequences will determine whether or
not the two LDH types are homologous [229]. In
any case, D-Iactate can be metabolized in some
circumstances even in animals that possess only Lspecific LDH. Mammalian liver, in fact, can turn
over D-Iactate IS-fold faster than L-Iactate. This is
of particular importance in the ruminants, where
the D-Iactate produced in the rumen by symbiontic bacteria is oxidized with the help of
mitochondrial D-2-bydroxy-acid dehydrogenases,
which are found especially in the brain cortex but
also in the heart and liver [92].
D-Specific LDHs have been isolated from various animals and have been characterized: from
the xiphosuran Limulus polyphemus, the barnacle Balanus nubilis, the polychaete Nereis
virens, the cockle Cardium edule and the snails
Helix pomatia, H. aspersa, Haliotis cracherodii
and Achatina achatina [27,70,261]. The majority
of D-specific LDHs are dimers of 70-80 kDa. The
enzyme from Helix aspersa was described earlier
as a tetramer but, more recently, was described as
a dimer. The D-specific LDHs of the barnacle
Balanus nubilis and the snail Achatina achatina
are, however, tetrameric [261]. In their general
catalytic properties, most of the D-specific invertebrate LDHs lie intermediate between the heart
and muscle types of the vertebrates. Some, e.g.
from Limulus, Haliotis and Achatina, are inhibited by pyruvate but others, e.g. from Cardium
and Helix aspersa, are not [27, 261]. At least the
enzymes from Balanus, Haliotis and Helix
aspersa show relatively high activity against 2keto- and 2-hydroxybutyrate.
Limulus polyphemus has a complicated system
of tissne-specific isoenzymes which must be considered in relation to processing of the end products arising from activity-dependent anaerobiosis.
Altogether, there are four different LDH subunits, A-D, which form six dimeric isoenzymes: a
"heart-type triad" (AA, AB, BB) and a "muscletype triad" (CC, CD, DD). The muscle-type triad
predominates in the skeletal muscles, and the
heart type predominates in the hepatopancreas;
the heart contains more of the muscle-type LDH
than of the heart type. The lactate affinity and the
pyruvate sensitivity decrease in the order AB >
BB > CD > DD. Under physiological conditions, lactate prodl).~tion is clearly preferred by
the muscle type, whereas the predominant heart
type of the hepatopancreas is active in both direc-