on this interpretation. It is in many cases not possible to explain why one tissue preferentially contains A and another tissue contains B. For example, the ratio of A:B in mammalian liver varies
with the species from 10:90 to 90:10. B predominates in bovine eye lens but A is the predominant
type in both rat and rabbit lenses. Embryonal
mammalian tissues contain almost exclusively ~,
although lactate is preferentially oxidized [102].
Like other enzymes, the LDHs may also be
adapted to particular internal or external conditions. The homotetrameric LDHS ~ and B4 of
the common hagfish Myxine glutinosa and Eptatretus cirrhatus have almost identical kinetic properties, corresponding to those of ~ from the skeletal muscles of other vertebrates. The isoenzyme
B4, present in the heart, is apparently specifically
adapted to the necessity for anaerobic glycolysis
in the heart muscle [8]. In turtles of the genus
Pseudemys, the B4 of the heart has all the characteristics of muscle type ~; this may be interpreted as an adaptation to the diving habit of this
animal. But, despite similar behaviour, the species Caretta caretta has a typical B4 in its heart
muscle [5]. In marine elasmobranchs that retain
urea in order to regulate their osmolality, A4
shows only the low pyruvate affinity and inhibition typical of the muscle enzyme in the presence
of physiological urea concentrations of about
400 ""mol/l; the LDHs from the freshwater ray
Potamotrygon sp. or marine teleosts do not have
this property. The muscle LDH of teleosts is very
suitable for investigating adaptation to a high
hydrostatic pressure. Compared with the muscle
enzyme of the coastal species Sebastodes alascanus, the A4 of the deep-sea species S. altivelis has
a much lower pressure sensitivity for substrate
and cosubstrate binding. This is most likely due to
the fact that the LDH of the coastal species has a
histidine at position 115, the ionization of which is
pressure sensitive, whereas the LDH of the deepsea species has an asparagine in this position
[230].
The primary spermatocytes of mammals and
birds contain LDH-X, which is made up tetramerically from a third type (C) of LDH subunit. C4
makes up more than 80 % of LDH in mammalian
sperm; it is present in much lower amounts in
avian sperm, and is completely absent from
turkey sperm. The sperms of the monotrome
mammals also lack C4 [211, 278]. LDH-C4 differs
in many specific ways from A4 and B4; it is localized in the mitochondria and involved in the
transport of reduction equivalents through the
mitochondrial membrane. It can also process a14.11.1 Lactate Dehydrogenases of Vertebrates
543
keto acids or a-hydroxy acids with more than
three C atoms. A similar broad specificity is found
in only one B4, that of the lizard Gecko gecko. C4
shows large species-specific differences in its catalytic properties: bovine, guinea-pig and rabbit C4
are only active with a-ketobutyrate; the human,
pig, goat and pigeon enzyme also metabolizes
acids with five or six C atoms, but only with a low
affinity; the C4 from the rat and mouse has a high
affinity for Cs and C6 acids and also a high affinity
for branched a-keto acids. The pyruvate inhibition of C4 of the rat, mouse and pigeon exceeds
that of B4, is about the same in humans, guineapigs and rabbits, and is absent in the cow, goat
and pig [39].
An LDH-C subunit is found in addition to A
and B in all Actinopterygii, i.e. the Chondrostei,
Polypteri, Holostei and Teleostei, but is absent
from the agnathans, elasmobranchs, dipnoans
and crossopterygians. It appears also that the C
subunit is lacking in the reptiles and amphibians
[149]. The C subunit is present in many different
tissues of the ancient Actinopterygii, i.e. the
Chondrostei, Polypteri and Holostei, and in
primitive teleosts such as the Elopiformes,
Anguilliformes and Osteoglossiformes; in the
remaining teleosts it is found only in neuronal tissues such as the retina and brain and less often in
the liver (Table 14.7) [104, 118, 149, 202]. The C4
from cod liver, like that of mammalian sperm, is
also active with mono- and bicarbonic acids with
five C atoms [202]. Fish liver C4 always has a net
positive charge and lies cathodic of A4 and B4.
The retina-brain enzyme is usually the most negatively charged but may also be found between ~
and B4 or even cathodic to them [38, 149]. Fish C
can form heterotetramers with A and B; the frequently observed restriction of A and B hybridization in fish is sometimes loosened in the presence of the C subunit. Thus, the eye and mesencephalon of Poecilia latipinna and P. velifera contain CA, CB and CAB heterotetramers in addition to ~, B4 and C4, but they contain no AB
hybrids.
The amino acid sequences are known for a
series of vertebrate LDHs: Squalus acanthias A,
chicken A and B, and all three subunits of various
mammals. These sequences have identical amino
acids at 60-90 % of their 330 positions, are thus
clearly homologous, and probably arose via
duplications of the same ancestral gene. The
greater similarity between subunits of the same
type in different species than between different
subunits in the same species indicates that the
isoenzymes arose very early in the evolution of
with the species from 10:90 to 90:10. B predominates in bovine eye lens but A is the predominant
type in both rat and rabbit lenses. Embryonal
mammalian tissues contain almost exclusively ~,
although lactate is preferentially oxidized [102].
Like other enzymes, the LDHs may also be
adapted to particular internal or external conditions. The homotetrameric LDHS ~ and B4 of
the common hagfish Myxine glutinosa and Eptatretus cirrhatus have almost identical kinetic properties, corresponding to those of ~ from the skeletal muscles of other vertebrates. The isoenzyme
B4, present in the heart, is apparently specifically
adapted to the necessity for anaerobic glycolysis
in the heart muscle [8]. In turtles of the genus
Pseudemys, the B4 of the heart has all the characteristics of muscle type ~; this may be interpreted as an adaptation to the diving habit of this
animal. But, despite similar behaviour, the species Caretta caretta has a typical B4 in its heart
muscle [5]. In marine elasmobranchs that retain
urea in order to regulate their osmolality, A4
shows only the low pyruvate affinity and inhibition typical of the muscle enzyme in the presence
of physiological urea concentrations of about
400 ""mol/l; the LDHs from the freshwater ray
Potamotrygon sp. or marine teleosts do not have
this property. The muscle LDH of teleosts is very
suitable for investigating adaptation to a high
hydrostatic pressure. Compared with the muscle
enzyme of the coastal species Sebastodes alascanus, the A4 of the deep-sea species S. altivelis has
a much lower pressure sensitivity for substrate
and cosubstrate binding. This is most likely due to
the fact that the LDH of the coastal species has a
histidine at position 115, the ionization of which is
pressure sensitive, whereas the LDH of the deepsea species has an asparagine in this position
[230].
The primary spermatocytes of mammals and
birds contain LDH-X, which is made up tetramerically from a third type (C) of LDH subunit. C4
makes up more than 80 % of LDH in mammalian
sperm; it is present in much lower amounts in
avian sperm, and is completely absent from
turkey sperm. The sperms of the monotrome
mammals also lack C4 [211, 278]. LDH-C4 differs
in many specific ways from A4 and B4; it is localized in the mitochondria and involved in the
transport of reduction equivalents through the
mitochondrial membrane. It can also process a14.11.1 Lactate Dehydrogenases of Vertebrates
543
keto acids or a-hydroxy acids with more than
three C atoms. A similar broad specificity is found
in only one B4, that of the lizard Gecko gecko. C4
shows large species-specific differences in its catalytic properties: bovine, guinea-pig and rabbit C4
are only active with a-ketobutyrate; the human,
pig, goat and pigeon enzyme also metabolizes
acids with five or six C atoms, but only with a low
affinity; the C4 from the rat and mouse has a high
affinity for Cs and C6 acids and also a high affinity
for branched a-keto acids. The pyruvate inhibition of C4 of the rat, mouse and pigeon exceeds
that of B4, is about the same in humans, guineapigs and rabbits, and is absent in the cow, goat
and pig [39].
An LDH-C subunit is found in addition to A
and B in all Actinopterygii, i.e. the Chondrostei,
Polypteri, Holostei and Teleostei, but is absent
from the agnathans, elasmobranchs, dipnoans
and crossopterygians. It appears also that the C
subunit is lacking in the reptiles and amphibians
[149]. The C subunit is present in many different
tissues of the ancient Actinopterygii, i.e. the
Chondrostei, Polypteri and Holostei, and in
primitive teleosts such as the Elopiformes,
Anguilliformes and Osteoglossiformes; in the
remaining teleosts it is found only in neuronal tissues such as the retina and brain and less often in
the liver (Table 14.7) [104, 118, 149, 202]. The C4
from cod liver, like that of mammalian sperm, is
also active with mono- and bicarbonic acids with
five C atoms [202]. Fish liver C4 always has a net
positive charge and lies cathodic of A4 and B4.
The retina-brain enzyme is usually the most negatively charged but may also be found between ~
and B4 or even cathodic to them [38, 149]. Fish C
can form heterotetramers with A and B; the frequently observed restriction of A and B hybridization in fish is sometimes loosened in the presence of the C subunit. Thus, the eye and mesencephalon of Poecilia latipinna and P. velifera contain CA, CB and CAB heterotetramers in addition to ~, B4 and C4, but they contain no AB
hybrids.
The amino acid sequences are known for a
series of vertebrate LDHs: Squalus acanthias A,
chicken A and B, and all three subunits of various
mammals. These sequences have identical amino
acids at 60-90 % of their 330 positions, are thus
clearly homologous, and probably arose via
duplications of the same ancestral gene. The
greater similarity between subunits of the same
type in different species than between different
subunits in the same species indicates that the
isoenzymes arose very early in the evolution of