Triose phosphate isomerase (TIM) is the most
active glycolysis enzyme in the insects and vertebrates (Table 14.1). This enzyme not only introduces dihydroxyacetone phosphate to glycolytic
degradation via glyceraldehyde phosphate but
can also function in the opposite direction as the
starting point for the formation of glycerol
phosphate, which is required for lipid and glycerol metabolism as well as for the aglycerophosphate cycle. TIM is always a homodimer with subunits of 247-249 amino acids and
27-28 kDa. Sequence comparisons point to a
relatively slow rate of evolution; compared with
the human sequence, the rabbit sequence shows
16 differences, the chicken sequence 38, and that
of Latimeria 80, but the bacteria sequence shows
170 differences [145]. The TIM of the Kinetoplastida is located in the glycosomes together with
eight other enzymes of glycolysis and glycerol
metabolism. The enzyme of Trypanosoma brucei
differs at 48-52 % of positions from the vertebrate enzyme but is not significantly different in its
kinetic-regulatory properties [128, 159]. Phosphoglycerate kinase (PGK) has mainly been
investigated in the mammals, although the
enzyme isolated from the halibut Hippoglossus
stenolepis has been the subject of studies of the
reaction mechanism [108]. The mammals possess
two isoenzymes of PGK. PGK-1, which is found
in all cells, is encoded by one gene on the X
chromosome; the human sequence (417 amino
acids) differs from that of the horse (416 amino
acid) at only 14 positions. The human and murine
PGK-2, as in some other mammals, is restricted
to the testis and sperm; it is encoded by an intronless gene that arose as a retroposon from a transcript of the PGK-1 gene. There is a further
human PGK-1 retroposon that has become nonfunctional due to several nonsense mutations
[152]. In the dog, fox and kangaroo PGK-2 is
found in other tissues in addition to the testis.
The kinetoplastids Trypanosoma brucei and Crithidia Jasciculata have three PGK genes, one of
which encodes the glycosomal PGK and a second
encodes the cytosolic enzyme; the protein product of the third gene has not yet been identified.
The two enzymes of T. brucei agree at 93 % of
positions, but the glycosomal enzyme has a more
positive charge and a C-terminal extension of 20
amino acids [133].
The phosphoglycerate mutases and 2,3bispbospboglycerate mutases belong to a family
of multifunctional enzymes which catalyse various reactions between phosphoglycerate (PG)
and bisphosphoglycerate (BPG):
14.8 Further Glycolysis Enzymes
533
1. Mutase reaction:
2. Synthase reaction:
3-PG + 2,3-BPG ~
2,3-BPG + 2-BG.
1,3-BPG + 3-PG ~ 3PG + 2,3-BPG.
3. Phosphatase reaction: 1,3-BPG ~ 3-PG + Pi.
The phosphoglycerate mutases (PGM; EC
5.4.2.1) are enzymes with predominantly mutase
activity, and the bisphosphoglycerate mutases
(BPGM; EC 2.7.5.4) are those which, above all,
catalyse the synthesis and cleavage of 2,3-BPG.
The agnathans have only one PGM, whereas all
other vertebrates, with the exception of the birds,
have several homo- or heterodimeric PGMs with
two types of subunit known as muscle type (M)
and brain type (B). One of the PGM genes has
been silenced during the evolution of the birds.
Skeletal muscle always contains MM; the liver,
kidney and brain contain mainly BB; and the
heart contains MM, MB and BB. B always
appears before M in ontogeny. The BPGM subunit E is expressed only in erythroid cells. The
activity of the homodimer EE in erythrocytes
leads to high concentrations of 2,3-BPG, which
reduces the oxygen affinity of haemoglobin to
physiological values. The human subunits B, M
and E agree in about 46 % of their amino acids
[30, 66, 134].
The enolases are dimers of non-covalently linked subunits of 47 kDa. Three different types of
subunit (a, ~, y) are found in the mammals and
birds; these show about 80 % sequence agreement with each other and form heterodimers. The
a and ~ subunits are found in many different tissues, whereas y is expressed only in neurons. In
embryonal muscle, aa is formed initially but is
replaced during myogenesis by ~~. Whereas in
adult skeletal muscle almost all the enolase activity is due to ~~, the smooth muscle and heart
muscle retain larger proportions of aa [75, 127,
151, 180]. The frog Xenopus laevis also has three
types of enolase subunit but these show a tissue
distribution different to that of the higher vertebrates [227]. The enolase from Drosophila melanogaster, which is the only invertebrate enolase to
have been sequenced so far, is similar in sequence
to the mammalian subunits a and y [15].
active glycolysis enzyme in the insects and vertebrates (Table 14.1). This enzyme not only introduces dihydroxyacetone phosphate to glycolytic
degradation via glyceraldehyde phosphate but
can also function in the opposite direction as the
starting point for the formation of glycerol
phosphate, which is required for lipid and glycerol metabolism as well as for the aglycerophosphate cycle. TIM is always a homodimer with subunits of 247-249 amino acids and
27-28 kDa. Sequence comparisons point to a
relatively slow rate of evolution; compared with
the human sequence, the rabbit sequence shows
16 differences, the chicken sequence 38, and that
of Latimeria 80, but the bacteria sequence shows
170 differences [145]. The TIM of the Kinetoplastida is located in the glycosomes together with
eight other enzymes of glycolysis and glycerol
metabolism. The enzyme of Trypanosoma brucei
differs at 48-52 % of positions from the vertebrate enzyme but is not significantly different in its
kinetic-regulatory properties [128, 159]. Phosphoglycerate kinase (PGK) has mainly been
investigated in the mammals, although the
enzyme isolated from the halibut Hippoglossus
stenolepis has been the subject of studies of the
reaction mechanism [108]. The mammals possess
two isoenzymes of PGK. PGK-1, which is found
in all cells, is encoded by one gene on the X
chromosome; the human sequence (417 amino
acids) differs from that of the horse (416 amino
acid) at only 14 positions. The human and murine
PGK-2, as in some other mammals, is restricted
to the testis and sperm; it is encoded by an intronless gene that arose as a retroposon from a transcript of the PGK-1 gene. There is a further
human PGK-1 retroposon that has become nonfunctional due to several nonsense mutations
[152]. In the dog, fox and kangaroo PGK-2 is
found in other tissues in addition to the testis.
The kinetoplastids Trypanosoma brucei and Crithidia Jasciculata have three PGK genes, one of
which encodes the glycosomal PGK and a second
encodes the cytosolic enzyme; the protein product of the third gene has not yet been identified.
The two enzymes of T. brucei agree at 93 % of
positions, but the glycosomal enzyme has a more
positive charge and a C-terminal extension of 20
amino acids [133].
The phosphoglycerate mutases and 2,3bispbospboglycerate mutases belong to a family
of multifunctional enzymes which catalyse various reactions between phosphoglycerate (PG)
and bisphosphoglycerate (BPG):
14.8 Further Glycolysis Enzymes
533
1. Mutase reaction:
2. Synthase reaction:
3-PG + 2,3-BPG ~
2,3-BPG + 2-BG.
1,3-BPG + 3-PG ~ 3PG + 2,3-BPG.
3. Phosphatase reaction: 1,3-BPG ~ 3-PG + Pi.
The phosphoglycerate mutases (PGM; EC
5.4.2.1) are enzymes with predominantly mutase
activity, and the bisphosphoglycerate mutases
(BPGM; EC 2.7.5.4) are those which, above all,
catalyse the synthesis and cleavage of 2,3-BPG.
The agnathans have only one PGM, whereas all
other vertebrates, with the exception of the birds,
have several homo- or heterodimeric PGMs with
two types of subunit known as muscle type (M)
and brain type (B). One of the PGM genes has
been silenced during the evolution of the birds.
Skeletal muscle always contains MM; the liver,
kidney and brain contain mainly BB; and the
heart contains MM, MB and BB. B always
appears before M in ontogeny. The BPGM subunit E is expressed only in erythroid cells. The
activity of the homodimer EE in erythrocytes
leads to high concentrations of 2,3-BPG, which
reduces the oxygen affinity of haemoglobin to
physiological values. The human subunits B, M
and E agree in about 46 % of their amino acids
[30, 66, 134].
The enolases are dimers of non-covalently linked subunits of 47 kDa. Three different types of
subunit (a, ~, y) are found in the mammals and
birds; these show about 80 % sequence agreement with each other and form heterodimers. The
a and ~ subunits are found in many different tissues, whereas y is expressed only in neurons. In
embryonal muscle, aa is formed initially but is
replaced during myogenesis by ~~. Whereas in
adult skeletal muscle almost all the enolase activity is due to ~~, the smooth muscle and heart
muscle retain larger proportions of aa [75, 127,
151, 180]. The frog Xenopus laevis also has three
types of enolase subunit but these show a tissue
distribution different to that of the higher vertebrates [227]. The enolase from Drosophila melanogaster, which is the only invertebrate enolase to
have been sequenced so far, is similar in sequence
to the mammalian subunits a and y [15].