trans

THE AEROBIC/ANAEROBIC TRANSITION DURING HELMINTH DEVELOPMENT 353
Perhaps more importantly, these studies have
most often been conducted in air (about 20%
oxygen), when oxygen tensions of 1–2% would
probably be much more physiological.
In A. suum muscle mitochondria, perhaps
the most anaerobic of all helminth mitochondria,
reduced cytochrome c oxidase activity is
barely detectable and oxygen utilization results
exclusively in the formation of hydrogen peroxide.
In fact, the ratio of Complex II to Complex
III is about 100 times greater than in rat
liver mitochondria, attesting to the importance
of NADH-dependent fumarate reduction in
the ascarid organelle. Substantial peroxide
formation has also been observed in mitochondria
isolated from other helminths, such as
H. diminuta and Ascaridia galli. In isolated
A. suum mitochondria, no additional energy
generation appears to be associated with oxygen
uptake, but succinate formation is slightly
reduced, suggesting that oxygen uptake in
these experiments may be unphysiological
and simply the result of its direct reaction with
the flavin moiety of the numerous flavoproteins
present in the helminth electron-transport
chain (i.e. the Fp subunit of complex II, ETF and
ETF dehydrogenase). In mammalian mitochondria,
these flavoproteins do not react readily
with oxygen, but their helminth counterparts
functioning in microaerobic environments may
not be under the same selective pressures to
maintain their oxygen insensitivity.
THE AEROBIC/ANAEROBIC
TRANSITION DURING
HELMINTH DEVELOPMENT
Two major generalizations may be made about
the developmental aspects of energy generation
in parasitic helminths. First, all adult helminths
use fermentative pathways to some extent and
excrete reduced organic acids as end-products
of carbohydrate metabolism, even in the presence
of oxygen. Second, at least some larval
stages of most helminths are aerobic with active
tricarboxylic acid cycles and CN-sensitive
respiration. Therefore, a marked aerobic–
anaerobic transition in energy metabolism
often occurs during the development of most
parasitic helminths. For example, schistosome
miracidia and cercariae are free-living and
aerobic. However, immediately after penetration
of the definitive host during development
from schistosomulum to adult, the schistosome
increasingly relies on glycolysis for energy
generation. Similarly, as mentioned above,
while excysted juvenile F. hepatica develop to
the adult, the ratio of tricarboxylic acid-cycle
activity to acetate and propionate formation
decreases, and there appears to be a direct
correlation between tricarboxylic acid-cycle
activity and the surface area of the fluke.
A similar relationship has been suggested
in nematodes. N. brasiliensis, H. contortus and
Ascaridia galli each exhibit significant cytochrome
oxidase staining in hypodermal mitochondria
found immediately beneath the
cuticle, but markedly decreased staining in
mitochondria from internal tissues, especially
in the larger helminths. Similar studies have
not been conducted in A. suum, but an oxygen
gradient in the worm has been suggested based
on other data. A. suum muscle and perienteric
fluid contain substantial amounts of hemoglobins
with extraordinarily high affinities for
oxygen (greater than 1000 times that of mammalian
hemoglobin). It has been suggested
that this hemoglobin functions as an O 2 buffer
system, maintaining a low but constant pO 2
internally (i.e. preventing oxygen toxicity, but
maintaining high enough oxygen tensions
for oxygen-dependent biosynthetic reactions).
For example, the synthesis of hydroxyproline
from proline for collagen synthesis catalyzed
by prolyl hydroxylase requires oxygen, and has
BIOCHEMISTRY AND CELL BIOLOGY: HELMINTHS