474
13 The Structure and Metabolism of Carbohydrates
specificity and, in addition to glucose-6-phosphate and galactose-6-phosphate, can oxidize
deoxyglucose-6-phosphate and glucose with
NAD+ or NADP+. The enzyme is designated
hexose-6-phosphate dehydrogenase by some
authors, but it is apparently identical to the glucose dehydrogenase (GDH) discovered in mammals in 1931. This enzyme has so far been found
only in vertebrates (mammals and teleosts) and
echinoderms. Of seven teleost species examined,
six possessed several GDHs in addition to
G6PDH; G6PDH was missing in Bathygobius
fuscus [148]. Whereas the enzyme is present in all
organs in the mammals, it is restricted to the liver
of the teleosts. Its function here may be to provide NADPH for the mixed-function oxidases
[24]. A unique reaction mechanism has been
described for the GDH from the teleost Fundulus
heteroclitus: in contrast to all other dehydrogenases, the glucose-6-phosphate here is bound before
the coenzyme [229].
G6PDH and GDH are in many respects very
different. In mammals, G6PDH is encoded in a
gene on the X chromosome, whereas the GDH
gene is autosomal. The G6PDH enzyme is localized in the cytoplasm and the vertebrate GDH is
membrane bound (microsomes). All G6PDH
enzymes from vertebrates and invertebrates are
activated by Mg2+ and inhibited by the SH
reagent p-chlormercuribenzoate (PCMB); the
GDH of the starfish Asterias amurensis, in contrast, is inhibited by Mg2+ and not affected by
PCMB. The liver GDHs from the rat and the
common carp are dimers with subunits of
96-99 kDa, whilst the G6PDHs from mammalian
and fish liver are dimers and tetramers, respectively, of 55-kDa subunits. Despite these differences, G6PDH and GDH appear to be homologous: the two enzymes in the starfish Asterias amurensis and those in the sea urchin Strongylocentrotus show clear relationships in immunoelectrophoresis. Although there is no discernible immunological relationship between the enzymes in
mammals, a relationship does emerge when the
amino acid sequences of the G6PDHs from rat
and carp liver and Strongylocentrotus ovary are
compared with the two liver GDHs [178]. The
oxidation of non-phosphorylated glucose to gluconolactone or gluconic acid can, in principle, be
catalysed by three different enzymes: the hydrogen peroxide-producing glucose oxidase (EC
1.1.3.4), glucose dehydrogenase (EC 1.1.1.47) and
the FAD-glucose dehydrogenase (EC 1.1.99.10).
Glucose oxidase has long been known as a component of bee honey. In Drosophila melanogaster,
an enzyme present in pupae of both sexes and in
the seminal vesicles of adult males is not glucose
oxidase, as was previously assumed, but FADglucose dehydrogenase, which was not known
previously from animals [45]. Two sugar dehydrogenases have been isolated from the hepatopancreas of the xiphosuran Limulus polyphemus; one
reduces especially D-xylose with NADP+ and the
other reduces L-galactose and L-fucose with
NAD+ or NADP+; both enzymes are found at
low activity in muscle [96].
6-Phosphogluconate dehydrogenases (6PGD H)
have been isolated from various organs and the
erythrocytes of mammals, from Drosophila melanogaster, and from Mytilus edulis [175]. These
enzymes all appear to be dimers of 100-105 kDa;
the Drosophila isoenzyme A consists of two different subunits of 53 and 55 kDa [83]. Similarly, at
least two different isoenzymes with somewhat different properties are found in Musca domestica.
The many investigations of 6PGDH show a much
lower level of polymorphism than that shown by
G6PDH (see Table 4.9, p. 134).
13.3.3 Biosynthesis of Fructose, Sugar
Alcohols and Glycerol
Fructose, which is found in mammals in the seminal fluid and in ungulates also in foetal blood at
high concentrations, arises in two steps from glucose via sorbitol as the intermediate (Fig. 13.11).
Glucose is reduced by the NADP-specific aldose
reductase to sorbitol, which is reoxidized to fructose by the action of NAD-specific sorbitol
dehydrogenase. High activities of aldose reductase are found in the seminal vesicles and the
ungulate placenta, and also in the eye lens. The
enzymes from the lens and placenta consist of 315
amino acids and are N-terminally acetylated.
They belong, together with the aldehyde reductase of the liver and placenta, the prostaglandin
F-synthase of the lung and the rho-crystallin of
the frog eye lens, to a family of monomeric,
NADPH-dependent oxidoreductases with a
Fig.13.ll. The sorbitol pathway
of fructose synthesis. 1, Aldose
reductase; 2, sorbitol dehydrogenase
Glucose
NAOPH+H+ l
NAOP+--~ CD
Sorbitol
NAO+ 1
NAOH+H+.®
Fructose
13 The Structure and Metabolism of Carbohydrates
specificity and, in addition to glucose-6-phosphate and galactose-6-phosphate, can oxidize
deoxyglucose-6-phosphate and glucose with
NAD+ or NADP+. The enzyme is designated
hexose-6-phosphate dehydrogenase by some
authors, but it is apparently identical to the glucose dehydrogenase (GDH) discovered in mammals in 1931. This enzyme has so far been found
only in vertebrates (mammals and teleosts) and
echinoderms. Of seven teleost species examined,
six possessed several GDHs in addition to
G6PDH; G6PDH was missing in Bathygobius
fuscus [148]. Whereas the enzyme is present in all
organs in the mammals, it is restricted to the liver
of the teleosts. Its function here may be to provide NADPH for the mixed-function oxidases
[24]. A unique reaction mechanism has been
described for the GDH from the teleost Fundulus
heteroclitus: in contrast to all other dehydrogenases, the glucose-6-phosphate here is bound before
the coenzyme [229].
G6PDH and GDH are in many respects very
different. In mammals, G6PDH is encoded in a
gene on the X chromosome, whereas the GDH
gene is autosomal. The G6PDH enzyme is localized in the cytoplasm and the vertebrate GDH is
membrane bound (microsomes). All G6PDH
enzymes from vertebrates and invertebrates are
activated by Mg2+ and inhibited by the SH
reagent p-chlormercuribenzoate (PCMB); the
GDH of the starfish Asterias amurensis, in contrast, is inhibited by Mg2+ and not affected by
PCMB. The liver GDHs from the rat and the
common carp are dimers with subunits of
96-99 kDa, whilst the G6PDHs from mammalian
and fish liver are dimers and tetramers, respectively, of 55-kDa subunits. Despite these differences, G6PDH and GDH appear to be homologous: the two enzymes in the starfish Asterias amurensis and those in the sea urchin Strongylocentrotus show clear relationships in immunoelectrophoresis. Although there is no discernible immunological relationship between the enzymes in
mammals, a relationship does emerge when the
amino acid sequences of the G6PDHs from rat
and carp liver and Strongylocentrotus ovary are
compared with the two liver GDHs [178]. The
oxidation of non-phosphorylated glucose to gluconolactone or gluconic acid can, in principle, be
catalysed by three different enzymes: the hydrogen peroxide-producing glucose oxidase (EC
1.1.3.4), glucose dehydrogenase (EC 1.1.1.47) and
the FAD-glucose dehydrogenase (EC 1.1.99.10).
Glucose oxidase has long been known as a component of bee honey. In Drosophila melanogaster,
an enzyme present in pupae of both sexes and in
the seminal vesicles of adult males is not glucose
oxidase, as was previously assumed, but FADglucose dehydrogenase, which was not known
previously from animals [45]. Two sugar dehydrogenases have been isolated from the hepatopancreas of the xiphosuran Limulus polyphemus; one
reduces especially D-xylose with NADP+ and the
other reduces L-galactose and L-fucose with
NAD+ or NADP+; both enzymes are found at
low activity in muscle [96].
6-Phosphogluconate dehydrogenases (6PGD H)
have been isolated from various organs and the
erythrocytes of mammals, from Drosophila melanogaster, and from Mytilus edulis [175]. These
enzymes all appear to be dimers of 100-105 kDa;
the Drosophila isoenzyme A consists of two different subunits of 53 and 55 kDa [83]. Similarly, at
least two different isoenzymes with somewhat different properties are found in Musca domestica.
The many investigations of 6PGDH show a much
lower level of polymorphism than that shown by
G6PDH (see Table 4.9, p. 134).
13.3.3 Biosynthesis of Fructose, Sugar
Alcohols and Glycerol
Fructose, which is found in mammals in the seminal fluid and in ungulates also in foetal blood at
high concentrations, arises in two steps from glucose via sorbitol as the intermediate (Fig. 13.11).
Glucose is reduced by the NADP-specific aldose
reductase to sorbitol, which is reoxidized to fructose by the action of NAD-specific sorbitol
dehydrogenase. High activities of aldose reductase are found in the seminal vesicles and the
ungulate placenta, and also in the eye lens. The
enzymes from the lens and placenta consist of 315
amino acids and are N-terminally acetylated.
They belong, together with the aldehyde reductase of the liver and placenta, the prostaglandin
F-synthase of the lung and the rho-crystallin of
the frog eye lens, to a family of monomeric,
NADPH-dependent oxidoreductases with a
Fig.13.ll. The sorbitol pathway
of fructose synthesis. 1, Aldose
reductase; 2, sorbitol dehydrogenase
Glucose
NAOPH+H+ l
NAOP+--~ CD
Sorbitol
NAO+ 1
NAOH+H+.®
Fructose