trans

ENVOI 137
unambiguously reflect the history of the
organisms or the history of their complete
metabolic machinery.
ENVOI
The description of core metabolism of a few
amitochondriate parasitic protists as presented
above clearly demonstrates that these organisms
are highly divergent from most eukaryotes
with typical mitochondria, including their
mammalian hosts. This divergence is apparent
not only in the metabolic consequences of the
absence of mitochondria, but also in the presence
of processes and enzymes found only
exceptionally in other eukaryotes. In terms of
applied parasitology, the most significant difference
is the central role of pyruvate:ferredoxin
oxidoreductase, the enzyme responsible for the
high and selective activity of 5-nitroimidazole
derivatives on amitochondriate parasites. It
remains to be seen whether the core metabolism
of these organisms will provide additional
leads to new drugs (Chapter 17).
This necessarily concise presentation might
give the false impression that we have a complete
and coherent understanding of amitochondriate
core carbohydrate metabolism. In
fact, we have nothing more than a skeleton
image that accounts for the bulk of carbon flow
and the formation of the major metabolic endproducts.
Many enzymes present have not been
characterized in detail. In the ongoing genome
projects new open reading frames are being
recognized that code for homologs of metabolic
enzymes of other organisms, but their putative
functions cannot be accommodated within our
current understanding. Another significant
shortcoming is that published metabolic carbon
and redox balance data for all amitochondriate
organisms are incomplete. While this
circumstance is easily explained by technical
difficulties presented by organisms that cannot
be grown on simple defined media, it hampers
the development of a comprehensive metabolic
map and makes forays into explorations of
metabolic regulation difficult.
Almost all the evidence presented here has
been collected from in vitro studies of organisms
maintained in bacteria-free (axenic) cultures.
Such cultures, however, do not reflect
closely the conditions in their natural habitats.
In addition it cannot be excluded that prolonged
cultivation under artificial conditions
can provoke changes in metabolism. While we
have rather clear ideas of certain metabolic
characteristics of the organisms studied, there
is always the caveat that we might have studied
only a restricted and possibly modified
subset of their metabolic capabilities.
The absence of mitochondria is often
equated with an ‘ancestral’ status of
these organisms. While this issue is much
debated, increasing evidence indicates that a
mitochondrion-related organelle was present
in the ancestors of amitochondriate eukaryotes
and that the lack of mitochondria is a
derived character, due to regressive evolution
by functional losses (Chapter 12). The ‘simplification’
of the metabolic machinery is probably
not a result of the establishment of a
parasitic lifestyle by the ancestors of amitochondriate
organisms, since similar metabolic
characters are present in their free-living relatives
that live in anaerobic or hypoxic sediments
of diverse water bodies. This simplification
probably was advantageous in the transition
to parasitism in the metazoan gut, where
hypoxic conditions prevail. These events are,
however, shrouded in a veil of a distant past.
The data also disclose the existence of characters
that are difficult to relate to functional
losses, and indicate that these have been
acquired by horizontal gene transfers from
other, probably prokaryotic, organisms. The
BIOCHEMISTRY AND CELL BIOLOGY: PROTOZOA