9. SACCHARIDES: ALTERNATE ROUTES OF METABOLISM
437
reduced to 6-PGA rather than oxidized to the expected product, ribulose5-phosphate.
The alternate proposal, that 3-ketogluconate-6-phosphate may be
formed as an intermediate in the oxidation of 6-PGA, was favored by
Horecker and colleagues (93, 94) and by Racker (2), partly on the
basis of the analogy with isocitric and malic dehydrogenases. This theory
suffers from the uncertainty consequent upon the fact that the compound has not been tested because it is not available. Until this can
be done, the proposed mechanisms must await verification. Meanwhile,
it may seem reasonable to speculate that either or both 2-keto and
3-ketogluconate phosphates may function, depending upon the system
and conditions used; either of the products (R-5-P or Ru-5-P) can be
metabolized further by a suitable isomerase (see next section).
4. Pentose Phosphate Isomerase; Phosphoketopentose
Epimerase
Reactions 1 and 2 of Fig. 2 are actually more complicated than is
shown (95, 96); they should probably be represented as shown in
Fig. 4.
In these reactions an isomerization occurs between R-5-P and Ru-5-P
[enzyme:pentose phosphate isomerase (PPI)], and there is also an
epimerization of the keto sugars Ru-5-P and Xu-5-P [enzyme:phosphoketopentose epimerase (PKPE)]. The subsequent reaction involving
transketolase has been shown (97, 98) to act on Ru-5-P only after its
conversion into Xu-5-P. The latter enzyme was at first called a Waldenase (99), but on the basis of evidence for a 3-ketopentose phosphate
occurring as a minor product of the epimerization (95, 100) the name
epimerase seems to be preferred. Although the mechanism of the
epimerase reaction has not been determined, the formation of this
3-ketopentose phosphate as one of the products suggests the formation
(98) of a 2,3-enediol phosphate as intermediate, and revives (by analogy) the prospect of 3-ketogluconate serving as intermediate in 6-PGA
oxidation, as discussed in the preceding section.
Both the foregoing enzymes have been observed in animal tissues,
bacteria, and plants. The mode of action appears to be the same from
all sources. The aldo-ketopentose phosphate isomerase (PPI) enzyme
was discovered by Horecker et al. (94) in yeast. The reported equilibrium ratio varies from 0.3 for Ru-5-P:R-5-P in yeast (94) to 0.5 in red
cells (2a). In the PKPE reaction (101), the Xu-5-P:Ru-5-P ratio at
equilibrium was 1.5. Dische and Shigeura (102), using calculations upon
the enzyme from red cells and alfalfa (103), suggest that the various
phosphates may coexist in equilibrium in the approximate proportions
of 35% R-5-P, 16.5% Ru-5-P, 45.5% Xu-5-P, and 3% 3-ketopentose phos-
437
reduced to 6-PGA rather than oxidized to the expected product, ribulose5-phosphate.
The alternate proposal, that 3-ketogluconate-6-phosphate may be
formed as an intermediate in the oxidation of 6-PGA, was favored by
Horecker and colleagues (93, 94) and by Racker (2), partly on the
basis of the analogy with isocitric and malic dehydrogenases. This theory
suffers from the uncertainty consequent upon the fact that the compound has not been tested because it is not available. Until this can
be done, the proposed mechanisms must await verification. Meanwhile,
it may seem reasonable to speculate that either or both 2-keto and
3-ketogluconate phosphates may function, depending upon the system
and conditions used; either of the products (R-5-P or Ru-5-P) can be
metabolized further by a suitable isomerase (see next section).
4. Pentose Phosphate Isomerase; Phosphoketopentose
Epimerase
Reactions 1 and 2 of Fig. 2 are actually more complicated than is
shown (95, 96); they should probably be represented as shown in
Fig. 4.
In these reactions an isomerization occurs between R-5-P and Ru-5-P
[enzyme:pentose phosphate isomerase (PPI)], and there is also an
epimerization of the keto sugars Ru-5-P and Xu-5-P [enzyme:phosphoketopentose epimerase (PKPE)]. The subsequent reaction involving
transketolase has been shown (97, 98) to act on Ru-5-P only after its
conversion into Xu-5-P. The latter enzyme was at first called a Waldenase (99), but on the basis of evidence for a 3-ketopentose phosphate
occurring as a minor product of the epimerization (95, 100) the name
epimerase seems to be preferred. Although the mechanism of the
epimerase reaction has not been determined, the formation of this
3-ketopentose phosphate as one of the products suggests the formation
(98) of a 2,3-enediol phosphate as intermediate, and revives (by analogy) the prospect of 3-ketogluconate serving as intermediate in 6-PGA
oxidation, as discussed in the preceding section.
Both the foregoing enzymes have been observed in animal tissues,
bacteria, and plants. The mode of action appears to be the same from
all sources. The aldo-ketopentose phosphate isomerase (PPI) enzyme
was discovered by Horecker et al. (94) in yeast. The reported equilibrium ratio varies from 0.3 for Ru-5-P:R-5-P in yeast (94) to 0.5 in red
cells (2a). In the PKPE reaction (101), the Xu-5-P:Ru-5-P ratio at
equilibrium was 1.5. Dische and Shigeura (102), using calculations upon
the enzyme from red cells and alfalfa (103), suggest that the various
phosphates may coexist in equilibrium in the approximate proportions
of 35% R-5-P, 16.5% Ru-5-P, 45.5% Xu-5-P, and 3% 3-ketopentose phos-