trans

340 ENERGY METABOLISM IN HELMINTHS
organic acids in addition to oxygen as terminal
electron acceptors, and cyanide-insensitive
electron-transport-associated ATP synthesis is
coupled to the excretion of reduced organic
acids as end-products of carbohydrate metabolism.
The present chapter will consider these
two metabolic strategies separately.
GLYCOGEN METABOLISM
Glycogen is present in all parasitic helminths,
but its function can vary depending on species.
Intestinal helminths, such as Ascaris suum,
display a predominantly anaerobic metabolism
and use stored glycogen as a key energy
reserve. Not surprisingly, helminth glycogen
levels fluctuate with host feeding, and glycogen
stored during feeding is rapidly utilized
when the host is in the post-absorptive state.
In contrast, blood-dwelling parasites, like adult
schistosomes, continuously reside in a glucoserich
environment, and the function of glycogen
storage and metabolism in these organisms is
still not completely clear.
Helminth glycogen synthesis is fuelled exclusively
by host-derived carbohydrate (primarily
glucose). Adult parasitic helminths are incapable
of gluconeogenesis, except from intermediates
at the level of triose phosphates.
In mammals, gluconeogenesis operates when
glucose is scarce, and then only in the presence
of both a gluconeogenic substrate and second
substrate other than carbohydrate that can be
used for the production of the energy required
for gluconeogenesis. These conditions are not
found in adult parasitic helminths, as they rely
almost exclusively on carbohydrate for energy
generation. In contrast, gluconeogenesis may
operate in aerobic larval stages that use substrates
other than carbohydrates for energy
generation. For example, during the development
of A. suum larvae within the eggshell,
glycogen is resynthesized from long-chain fatty
acids through the glyoxylate cycle (see Section
on the Aerobic/Anaerobic Transition during
Helminth Development). This cycle, which is
typically found in microorganisms and plants,
has not been demonstrated in other parasitic
helminths, although it is also present in the
free-living nematode, Caenorhabditis elegans.
The simultaneous synthesis and degradation
of glycogen would result in substrate
cycling and a loss of energy. Therefore, not
surprisingly, the activities of the key enzymes
regulating glycogen metabolism, glycogen synthase
and glycogen phosphorylase, are under
tight regulatory control. These enzymes have
been thoroughly studied only in adult A. suum
muscle, where glycogen levels are up to 12-
fold greater than in mammalian muscle and
can account for up to 50% of the dry weight
of the tissue. In adult A. suum glycogen is
stored during periods of host feeding and is
metabolized during host fasting. Both enzymes
from adult A. suum muscle are remarkably
similar in many respects to the well studied
mammalian enzymes. For example, both glycogen
phosphorylase and glycogen synthase
activities are regulated by reversible phosphorylation/dephosphorylation,
as are their
mammalian counterparts. However, a novel
form of glycogen synthase (GSII) has been identified
in A. suum, and the regulation of the
GSII complex, which appears to function as an
intermediate between glycogenin and mature
glycogen in muscle, may be important in
maintaining the high glycogen levels in adult
A. suum muscle. In contrast, the regulation
of glycogen metabolism in other parasitic
helminths is not always as tightly controlled.
For example, in adult Schistosoma mansoni,
glycogen degradation in vitro occurs even
during periods of net synthesis, and vice versa.
Similarly, glycogen reserves in schistosomes
residing inside the veins of their hosts do not
BIOCHEMISTRY AND CELL BIOLOGY: HELMINTHS