trans

MITOCHONDRIAL METABOLISM AND ENERGY GENERATION 347
forms primarily propionate and acetate as endproducts.
In the nematode A. suum, acetate
and propionate are further metabolized to the
branched-chain fatty acids, 2-methylbutanoate
and 2-methylpentanoate, through a pathway
similar to reversal of -oxidation, and a complex
mixture of acetate, propionate, succinate,
2-methylbutanoate, and 2-methylpentanoate
is excreted as end-products. Branched-chain
fatty acid formation provides an additional
avenue for the oxidation of excess reducing
power, and is potentially an additional site of
electron-transport-associated ATP synthesis
coupled to the NADH-dependent reduction of
2-methyl branched-chain enoyl CoAs. Finally,
some organisms, such as H. contortus and
Trichostrongylus colubriformis, form neutral
volatile compounds, such as propanol. The
mechanism and site of propanol formation
are not well understood, but since the reduction
of propionate to propanol is unlikely, the
pathway probably involves propionyl CoA as
an intermediate. The factors dictating the types
and ratios of anaerobic end-products are
complex. However, habitat and worm size (as a
function of surface to volume ratio), certainly
play key roles in the selection of pathways used
to generate energy and maintain redox balance,
especially as they affect the availability of
oxygen and glucose. In addition, the pK a s for
many of these end-products, such as succinate
or especially the volatile organic acids,
are much lower than that of lactate, which
may facilitate their excretion or minimize their
effects on tissue acidification.
Ascaris suum is one of the few unusually
large helminths from which substantial
amounts of homogeneous tissue can be dissected
for use in the isolation of mitochondria
or protein purification, and for this reason
its metabolism is probably the best studied of
all of the parasitic helminths. However, it is
important to note that because of its very large
size A. suum is atypical, and generalizations
from A. suum to its smaller cousins should be
made with caution. Most of the enzymes
involved in the dismutation of malate in anaerobic
mitochondria from adult A. suum body
wall muscle have been purified to homogeneity
and at least partially characterized. As mentioned
above, the tricarboxylic acid cycle is not
significant in these novel organelles and the
levels of citrate synthase, aconitase, isocitrate
dehydrogenase, and -ketoglutarate dehydrogenase
are low or barely detectable. In fact,
cytoplasmically generated malate, not pyruvate,
is the primary mitochondrial substrate.
Malate enters the mitochondrion through a
phosphate-dependent porter system, and a
portion is decarboxylated to pyruvate by the
action of an NAD -linked ‘malic’ enzyme, generating
reducing power in the form of NADH.
This intramitochondrial NADH then reduces
the remaining malate, via fumarate, to succinate.
In H. diminuta, ‘malic’ enzyme is NADP -
linked, and this helminth contains an active,
energy-linked, NADPH:NAD transhydrogenase
activity that converts NADPH to NADH.
Mitochondria from adult A. suum body wall
muscle catalyze the efficient, energy-linked,
NADH-dependent reduction of fumarate to
succinate (Figure 14.3). Complex I (NADH:
rhodoquinone oxidoreductase), a novel quinone,
rhodoquinone, and Complex II (succinate:
rhodoquinone oxidoreductase) are all
involved in NADH-dependent fumarate reduction.
In fact, all mitochondria are capable of
some succinate formation in the absence of
oxygen, but anaerobic helminth mitochondria
are modified to catalyze this reduction at a
much faster rate and generate additional energy
from the process. For example, although the
polypeptide composition of both the A. suum
Complex I and II are superficially similar to
those of their aerobic counterparts, the ratio of
fumarate reductase to succinate dehydrogenase
BIOCHEMISTRY AND CELL BIOLOGY: HELMINTHS