trans

168 ENERGY METABOLISM – APICOMPLEXA
FIGURE 7.10 The mannitol cycle in Eimeria tenella. This cycle constitutes a major branching point from glycolysis
in E. tenella. Copious amounts of mannitol are created within the avian host (body temperature 41°C) where
it may function as an energy source during sporulation in the environment (25°C). Given its absence from the
host, this cycle has been the subject of interest as a drug target, leading to the production of nitrophenide, a mannitol
1-phosphate dehydrogenase inhibitor that prevents mannitol production and leads to defective E. tenella
sporulation.
function(s) of the mannitol cycle in E. tenella
and other apicomplexans are not entirely clear
(as is also the case for fungi). It is interesting to
speculate that possible roles for mannitol production
may include the production of NADH
for electron transport and oxidative phosphorylation.
Alternatively, mannitol might act as
an osmoregulator or as a protectant under
conditions of oxidative or salt stress.
MEDICAL SIGNIFICANCE
Although virtually all of the activities involved
in apicomplexan carbohydrate metabolism
and electron transport are well known from
other systems, the pathways as a whole diverge
significantly from host species, and have
already proven useful as a target for chemotherapeutic
intervention. Features that distinguish
the Apicomplexa range from simple amino
acid changes in enzyme cofactor- or substratebinding
sites, to the presence of pathways
known from other organisms that are missing
in the human host. Malate:quinone oxidoreductase
was previously known only in a subset
of prokaryotes, floridean starch in red
algae, and the mannitol cycle in bacteria and
fungi.
The selective interaction of atovaquone
with the apicomplexan Complex III is already
being exploited in the clinic, and has proven
particularly useful in combination with the
antifolate proguanil (Chapter 17). Synthetic
peptides that mimic the homodimer interface
BIOCHEMISTRY AND CELL BIOLOGY: PROTOZOA