trans

DEVELOPMENTAL VARIATION AND CARBOHYDRATE STORAGE 165
Unlike the soluble malate dehydrogenase, MQO
is a membrane-bound flavoenzyme capable
of transferring electrons directly to ubiquinone
rather than to NAD .
The mechanism of acetyl coenzyme A
production in apicomplexan parasites is not
entirely clear. The P. falciparum genome
encodes a pyruvate dehydrogenase, but this
enzyme is likely associated with the plastid
(apicoplast) rather than cytoplasmic or mitochondrial
metabolism. Acetyl CoA is probably
synthesized from acetate using acetyl CoA synthetase
enzymes, two of which are encoded
in the parasite genome.
Interestingly, the C. parvum genome reveals
a pyruvate:ferredoxin oxidoreductase (PFO)
or pyruvate:NADP oxidoreductase (PNO)
homolog – a protein unique to this organism
within the apicomplexan lineage, and once
thought to be restricted to amitochondrial
eukaryotes such as Giardia lamblia and
Trichomonas vaginalis. This enzyme catalyzes
the anaerobic oxidation of pyruvate, and subsequent
transfer of electrons to ferredoxin (PFO)
or NADP (PNO). Pyruvate is decarboxylated
in the process, yielding acetyl coenzyme A.
DEVELOPMENTAL
VARIATION AND
CARBOHYDRATE STORAGE
The phylum Apicomplexa includes 5000
species, and this diverse group encompasses
many metabolic pathway variations. As
discussed above for Plasmodium spp., most
stages of all apicomplexans probably garner
their energy supply from glycolysis under
normal circumstances, secreting lactate as the
major end-product. Mitochondrial electron
transport has been detected in many species,
and is undoubtedly important for survival, but
as noted above, it is probable that electron
transport usually plays only a marginal role in
parasite ATP production. Glycolysis may be differentially
regulated at different life-cycle stages
however. Enzymes for carbohydrate storage
and polysaccharide utilization are also required
at specific stages of the life cycle in many apicomplexan
parasites that exhibit a period of
prolonged dormancy or encystation.
Stage-specific pathway variation
Studies on the regulation of energy metabolism
in Toxoplasma gondii have been aided by
the ability to cultivate both tachyzoite and
bradyzoite stage parasites in vitro. Rapidly
dividing tachyzoites are the primary cause of
morbidity and mortality in humans and animals.
Tachyzoites spontaneously differentiate
into bradyzoites at low frequency, and bradyzoites
also are capable of re-emerging as tachyzoites.
The host immune response destroys
T. gondii tachyzoites, but fails to eliminate the
slowly dividing bradyzoite ‘tissue cyst’ form,
which may remain viable in the brain, muscle,
and other tissues for the life of the host. Bradyzoites
(in undercooked meat) are probably the
major form of transmission to adult humans,
and recrudescence of latent tissue cysts is a
serious complication associated with immunodeficiency
(in AIDS, or in patients given
immunosuppressive treatments for organ
transplantation, or cancer chemotherapy).
Inhibitors of mitochondrial electron transport,
such as antimycin and myxothiazol, cause
the expression of bradyzoite-specific antigens
on the cell surface, suggesting that this stage
may rely on anaerobic glycolysis. Supporting
this view, succinate dehydrogenase activity is
not detected in bradyzoites. These observations
probably also explain the relatively low sensitivity
of bradyzoites to atovaquone.
Several glycolytic enzymes are differentially
expressed in tachyzoites vs. bradyzoites.
BIOCHEMISTRY AND CELL BIOLOGY: PROTOZOA