trans

136 ENERGY METABOLISM – ANAEROBIC PROTOZOA
unable to reduce metronidazole. Essentially
these lines become hydrogenosome deficient,
though the organelle itself and some of its
enzymes are not lost. The lack of hydrogenosomal
pyruvate metabolism is compensated by
increased lactate production in T. vaginalis and
ethanol production in Tr. foetus.
EVOLUTIONARY
CONSIDERATIONS
This chapter deals primarily with the biochemical
and functional aspects of the amitochondriate
metabolic machinery. The core
of this metabolism is a typical Embden–
Meyerhof–Parnas glycolytic pathway, as in
other eukaryotes, and none of the vast diversity
of carbohydrate catabolism seen in various
prokaryotes is present. The conservativism
of the overall pathway indicates that it has
been acquired by the common ancestor of all
eukaryotes.
The evolutionary relationships of the
enzymes participating in extended glycolysis
in amitochondriates, however, present a complex
picture. Several enzymes are of a different
type from those in multicellular eukaryotes,
a point alluded to above in the discussions of
amitochondriate core metabolism and the differences
between amitochondriate and mitochondriate
cells. In some cases isofunctional
enzymes of different amitochondriates belong
to different types. Each of the four organisms
discussed displays a different combination of
enzymes with different origins. A description
of these is beyond the scope of this chapter,
but three examples will make the point.
The first example is glucokinase, responsible
for hexose phosphorylation [reaction 1].
This activity in G. intestinalis and in T. vaginalis
is catalyzed by a typical glucokinase
with orthologs only in cyanobacteria and
proteobacteria. The glucokinase of E. histolytica,
in contrast, is closely related to hexokinases
found only in eukaryotes. These two enzyme
families derive from the same ancestral molecule
but are so divergent that only a few catalytically
important domains can be aligned to
each other.
A second example is phosphofructokinase
[reaction 3], an enzyme comprising several
easily distinguished protein families and subfamilies,
which probably separated early in
evolution. Of the two functional types (ATPand
PP i -linked), PP i -linked enzymes are characteristic
of the amitochondriate protists, but
in different species they belong to distantly
related subfamilies (clades). In addition, E. histolytica
also contains an ATP-PFK of unknown
functional significance.
The third example is glyceraldehyde
3-phosphate dehydrogenase [reaction 6]. The
enzymes of G. intestinalis and E. histolytica are
closely related to the glycolytic glyceraldehye
3-phosphate dehydrogenase of most eukaryotes,
while the enzyme from T. vaginalis and
other trichomonads forms a cluster separated
from other eukaryotes that is nested among
prokaryotic lineages.
This diversity in the nature of enzymes
catalyzing formally identical reactions is difficult
to interpret, but it indicates that each
step of the pathway can tolerate orthologous
or non-orthologous replacements of the corresponding
enzyme. The ecological significance
and the evolutionary processes behind
such replacements are yet to be elucidated.
Two major types of mechanisms can be
invoked: selective retention of one or another
enzyme that were present together in a common
ancestor, and horizontal gene transfer
from a donor to a recipient organism.
Different evolutionary relationships for individual
enzymes are a warning against assuming
that the history of any single gene could
BIOCHEMISTRY AND CELL BIOLOGY: PROTOZOA