trans

TREMATODES 307
Two schistosome glucose transporters have
been cloned. SGTP4 is homologous to the
human glucose transporter, GLUT1. It is only
detectable in schistosomula and adults (i.e.
stages where glucose is present in the environment),
and is localized exclusively in the tegument.
SGTP4 is integrated within membranous
vesicles that are assembled within the cytons.
The other glucose transporter, SGTP1, is localized
exclusively in the intestine (see below).
SGTP4 and SGTP1 have both been functionally
expressed and partially characterized in the
Xenopus oocyte system. This experimental
approach should facilitate a thorough comparison
of the biochemistry and pharmacology
of parasite and host glucose transporters, perhaps
setting the stage for the identification of
parasite-selective inhibitors of glucose transport
as leads for anthelmintic development.
Most glucose absorption occurs across the
dorsal tegument in male schistosomes; there is
no evidence for regional differences in females.
An intriguing aspect of glucose uptake is that,
for worm pairs in copula (the normal condition
in vivo), all or most glucose obtained by
the female is supplied by the male partner. In
addition, mated pairs absorb more glucose
than unmated schistosomes, even though the
total worm surface area exposed to the external
medium is much reduced in paired worms.
This increase in glucose uptake in pairs may
occur as a result of a greater number of transport
sites on the dorsal surface of the male.
Amino acid uptake by trematodes occurs primarily
across the tegument. Mechanical ligation
of the intestine or drug treatments that
induce regurgitation do not significantly affect
amino acid uptake kinetics. Amino acid absorption
by F. hepatica occurs by passive diffusion, as
uptake is linear over a wide range of concentrations
and there is no evidence for competitive
inhibition among related amino acids. In schistosomes,
it appears that methionine, glutamate,
arginine and alanine are absorbed across the
tegument by a combination of passive diffusion
and a carrier-mediated system. The number of
distinct amino acid uptake systems in schistosomes
is unknown, though there is evidence for
at least two and possibly three. These systems
have a high affinity for amino acids only, as
methionine uptake is not inhibited by other
organic compounds, and moving the amino
group to carbons adjacent to the -carbon
reduces the affinity of the transport system.
Trematodes do not synthesize cholesterol
de novo, but acquire it from the host. Uptake
occurs via the tegument, primarily at the dorsal
surface of males, and cholesterol is then
redistributed throughout the body. Cholesterol,
like glucose, is transferred between partners
in copula. Other lipids, including ceramide,
are also transported rapidly across the tegument.
Absorption may be restricted to distinct
patches of membrane on the schistosome surface.
Of particular interest are caveolae-like
microdomains found mainly in the tubercles
of male worms. In other eukaryotes, caveolae
serve as pockets in which signal transduction
occurs, via a linker protein called caveolin; this
protein has not been identified in schistosomes.
Osmotic/volume regulation
During the process of transformation from cercaria
to schistosomulum following penetration
of the host skin, schistosomes become highly
permeable to water. When placed in hyposmotic
medium, schistosomula and adult schistosomes
gain weight rapidly, then exhibit a
slow recovery to control weight levels. This
response indicates a capacity for osmoregulation,
and has been interpreted as an initial
osmotic uptake of water across the tegument
followed by a slower efflux of ions from the tissue,
with water following. In hyperosmotic
medium, schistosomes slowly lose weight due
to osmotic efflux of water. How trematodes
BIOCHEMISTRY AND CELL BIOLOGY: HELMINTHS