trans

222 PURINES AND PYRIMIDINES
whereas uracil and uridine are preferentially
taken up into uridylates.
Salvage enzymes that have been detected
in T. vaginalis are also different from those
found in T. foetus. UPRT levels are low, and
uracil is converted to uridine by UP. Uridine,
cytidine, and thymidine are all converted to
the monophosphate by pyrimidine NPTs.
No pyrimidine nucleoside kinases have been
detected in T. vaginalis. T. vaginalis also lacks
RR. Pyrimidine deoxynucleotides are obtained
by salvage of deoxynucleosides via a deoxynucleoside
phosphotransferase activity, which recognizes
both purine and pyrimidine substrates.
Giardia lamblia
G. lamblia is incapable of pyrimidine biosynthesis
but has extensive pyrimidine salvage
and interconversion capacities. The parasite
also lacks an RR activity and must therefore
salvage both deoxycytidine and thymidine.
A thymidine NPT has been analyzed, but
the route of deoxycytidine incorporation is
unknown.
Entamoeba histolytica
E. histolytica can incorporate orotate into
nucleic acids, possesses ATC activity, and can
grow in pyrimidine-depleted medium. Thus,
the parasite appears to be capable of pyrimidine
biosynthesis de novo. The ability to proliferate
axenically in pyrimidine-deficient
medium also implies that the parasite expresses
both RR and TS activities. E. histolytica can also
salvage pyrimidines, but the enzymes have not
been studied in detail.
Helminths
Although investigations have been limited
to representative organisms, all parasitic
helminths appear to be capable of pyrimidine
biosynthesis de novo. The most detailed
biochemical investigations have been accomplished
with S. mansoni, an organism in
which all of the pyrimidine biosynthetic
enzymes have been detected. Like mammalian
cells, the first three pyrimidine biosynthetic
enzymes appear to be components of
a multifunctional complex, the fourth appears
to be membrane-bound, and the last two
part of a bifunctional complex. S. mansoni
also appears to salvage pyrimidines, including
cytidine, uridine, thymidine, deoxycytidine,
orotate, and uracil. Enzyme activities that
have been described include phosphorylases,
phosphotransferases, and kinases for pyrimidine
nucleosides and PRTs for orotate and
uracil. The existence of RR activity is supported
by the conversion of radiolabeled
uracil into deoxynucleotides and the ability
of hydroxyurea, the RR inhibitor, to interfere
with DNA synthesis. Several lines of evidence
also support the existence of pyrimidine
biosynthesis and salvage in other trematodes,
including Fasciola gigantica, Clonorchis sinensis,
and Paragonimus ohirai. These include
detection of biosynthetic and salvage activities
in worm lysates and metabolic labeling
studies.
There is also good evidence for pyrimidine
biosynthesis in cestodes and nematodes. Five
of the six de novo enzymes have been measured
in the cestode Hymenolepis diminuta
and ATC was found in Moniezia benedeni.
Cestodes can also salvage pyrimidines, but
only a TK activity from H. diminuta has been
characterized. Five pyrimidine biosynthesis
enzymes have also been detected in the
nematodes Nippostrongylus brasiliensis and
Trichuris muris, and CPSII and ATC have been
found in Ascaris. TS and pyrimidine salvage
activities have also been observed in other
nematode species.
BIOCHEMISTRY AND CELL BIOLOGY: PROTOZOA