trans

354 ENERGY METABOLISM IN HELMINTHS
been identified in all helminths examined
to date. Whether oxygen can be used by tissues
other than muscle for energy generation
remains to be determined.
Helminth eggs leave the definitive host in
widely varying stages of development. Many
nematode eggs, such as those of A. suum,
are undifferentiated and require oxygen for
embryonation. Many cestode and trematode
eggs leave fully embryonated, suggesting that
embryonation occurs in the microaerobic
habitat of the host. When unembryonated
A. suum ‘eggs’ leave the host, cytochrome
oxidase activity and ubiquinone are barely
detectable and the ‘eggs’ appear to be transcriptionally
inactive. After about 48–72 h in
air, metabolism increases dramatically, fueled
intitially by glycogen and then by stored triacylglycerols,
as the worm begins a series of
larval molts within the eggshell resulting ultimately
in a quiescent infective larva. During
this process cytochrome oxidase activity
increases dramatically, the tricarboxylic acid
cycle and -oxidation are operative, and metabolism
is aerobic. A. suum is one of the few
metazoans capable of net glycogen synthesis
from triacylglycerols, and possesses a functional
glyoxylate cycle. At about day 10 of
development, the activities of malate synthase
and isocitrate lyase, two key enzymes in the
glyoxylate cycle, begin to increase dramatically,
triacylglycerol stores decrease, and
glycogen, consumed earlier in development,
is resynthesized. Once development is complete,
the metabolic rate of the infective larva
decreases significantly and the infective
‘eggs’ may remain dormant for long periods
until ingestion by the definitive host. These
quiescent larvae closely resemble the dauer
larva of many free-living nematodes, such as
C. elegans. Since dauer larva formation is linked
exclusively with the transition to the third stage
(L3) in all other nematodes, this quiescent
ascarid larva may actually be an L3 and not an
L2, as suggested by many of the early studies.
Little is known about the factors regulating
energy generation during this developmental
process or in the arrested infective larvae.
For example, the factors responsible for the
initial burst of transcription and the synthesis
of cytochrome oxidase, the regulation of
glyoxylate cycle activity, or the decreased
respiratory rate associated with dormancy are
poorly understood. Similarly, the triacylglycerols
of unembryonated eggs contain substantial
amounts of 2-methylbutanoate and
2-methylpentanoate, major products of carbohydrate
metabolism in adult muscle. However,
nothing is known about the relationship
between the enzymes catalyzing -oxidation
during early larval development and the reversal
of -oxidation in adult muscle. After ingestion
by the porcine host, larvae hatch in the
gut, then migrate through the liver to the
lungs. Larval metabolism during this transition
is aerobic and cyanide-sensitive. However,
after the L3 migrate from the lungs back to the
small intestine, they molt to the fourth stage
(L4), respiration becomes cyanide-insensitive,
and branched-chain fatty acids characteristic
of the adult begin to be excreted. As predicted,
the activities of enzymes associated with aerobic
metabolism decrease dramatically, while
those associated with anaerobic pathways
increase in an equally dramatic fashion. Interestingly,
many of the key enzymes regulating
these metabolic pathways appear to exist as
stage-specific isoforms.
Although we have a reasonably clear understanding
of how mitochondria from adult
helminths generate energy in the absence of
oxygen, much less is known about how mitochondrial
biogenesis is regulated during the
various aerobic/anaerobic transitions that
occur during helminth development. Clearly,
a variety of different strategies have been
BIOCHEMISTRY AND CELL BIOLOGY: HELMINTHS