trans

352 ENERGY METABOLISM IN HELMINTHS
A. suum. Alternatively, branched-chain fatty
acids may be more fastidiously excreted from
the organism, given their increased lipophilicity
and elevated pK a s.
On a broader scale, little is known about the
factors that regulate carbon flux and energy
generation during muscle contraction in either
flatworms or nematodes. Neither appears to
possess the ‘burst activity’ characterized in
other invertebrates, perhaps because predator
avoidance or the active pursuit of prey is not a
problem within the definitive host. However,
recently it has become clear that the regulation
of these processes may differ substantially
from similar processes in the host. For example,
during vertebrate muscle contraction, Ca 2
released from the sarcoplasmic reticulum is
readily accumulated by muscle mitochondria
through a high affinity transporter and activates
the Ca 2 -sensitive E1-phosphatase and
-ketoglutarate dehydrogenase complex, thus
effectively linking contraction and energy generation.
In contrast, mitochondria from A. suum
muscle are not uncoupled when incubated in
Ca 2 , suggesting a limited capacity for high
affinity Ca 2 uptake. In addition, the A. suum E1
phosphatase and F. hepatica -ketoglutarate
dehydrogenase are not stimulated by Ca 2 ,
suggesting that other factors are involved in
the coordination of these two processes.
Oxygen as a terminal electron
acceptor
Parasitic helminths have varying aerobic capacities,
depending primarily on their size and the
availability of oxygen in the surrounding environment.
For example, some small lumendwelling
nematodes, such as Nippostrongylus
brasiliensis, which reside close to the mucosa
where oxygen tensions are relatively high, have
a functional tricarboxylic acid cycle and rely
on oxygen as a terminal electron acceptor. In
contrast, the aerobic capacity of the juvenile
F. hepatica decreases with growth and is proportional
to its surface area, since in the absence
of a circulatory system oxygen must diffuse
directly from the liver parenchyma. In adult
F. hepatica, the outer aerobic layer of the parasite
accounts for only 1% of the total volume
and metabolism appears almost completely
anaerobic. Muscle mitochondria from unusually
large helminths, such as A. suum, which
reside in especially microaerobic habitats, such
as the vertebrate gut, form branched-chain fatty
acids and represent the anaerobic extreme.
Branched electron-transport chains have
been proposed for a number of helminth mitochondria,
with one branch leading to fumarate
as a terminal electron acceptor and the other
leading to oxygen through either classical,
CN-sensitive, cytochrome c oxidases or CNinsensitive,
peroxide-forming, terminal oxidases.
Certainly, the incubation of either intact
helminths or isolated mitochondrial preparations
in air alters the ratios of excreted fermentative
products, with acetate formation usually
increased and products of the reductive arm
of the pathway, such as succinate, propionate
and branched-chain fatty acids, reduced.
The shift in end-product formation probably
results from a decrease in intramitochondrial
NADH/NAD ratios. However, no terminal oxidase
has ever been isolated or purified from
any helminth mitochondrion, and at present
there are no definitive data confirming the
identity of any CN-insensitive terminal oxidase
in any parasitic helminth. The existence of
alternative oxidases has been inferred from
studies using inhibitors of oxygen uptake, such
as KCN or SHAM. These studies are limited by
our understanding of the specificity of these
inhibitors on helminth metabolism, and have
often been conducted using either fumarate
or oxygen as a terminal acceptor, without
measuring relative rates of energy generation.
BIOCHEMISTRY AND CELL BIOLOGY: HELMINTHS