trans

164 ENERGY METABOLISM – APICOMPLEXA
FIGURE 7.8 Proposed citric acid (TCA) cycle in Plasmodium falciparum. Although only a few of the enzyme
activities required for this process have been measured in P. falciparum extracts (e.g. succinate dehydrogenase,
isocitrate dehydrogenase), the parasite genome harbors genes for all eight proteins. The cycle may fully engage in
a clockwise fashion (aerobic) in stages of the parasite life cycle that are difficult to isolate and characterize
(e.g. within the mosquito midgut). At other times, portions of the cycle may flow counterclockwise to provide substrates
for biosynthetic pathways (such as succinyl-CoA for heme production). The malate:quinone oxidoreductase
is a membrane-bound flavoenzyme that, like succinate dehydrogenase, is capable of reducing ubiquinone directly.
increase in cristae formation observed during
gametogenesis and in sexual stage parasites
suggests a requirement for more robust mitochondria
in the mosquito midgut.
Citric acid (TCA) cycle
In mammalian systems, the eight-enzyme TCA
cycle produces NAD(P)H and FADH 2 , which feed
into the electron transport chain, leading to a
highly productive output of up to 15 molecules
of ATP per cycle. TCA enzyme activity has been
detected in P. falciparum (Figure 7.8), and
studies with digitonin-permeabilized P. berghei
(see above) have shown that many TCA cycle
intermediates are able to stimulate ATP
production. Succinate dehydrogenase is clearly
mitochondrial, but other activities, including
malate dehydrogenase, appear to be located
in the cytoplasm. Genomic data indicate that
both P. yoelii and P. falciparum contain genes
encoding all eight enzymes required to complete
the TCA cycle. The presence of a malate:
ubiquinone oxidoreductase (MQO) is of particular
interest, as this enzyme has not previously
been detected in any eukaryotic system.
BIOCHEMISTRY AND CELL BIOLOGY: PROTOZOA