trans

PURINE METABOLISM 217
FIGURE 9.8 Trichomonas vaginalis purine salvage and interconversion pathways. * Deoxynucleoside phosphotransferase.
All other enzyme identities are listed in Table 9.1.
that adenine and guanine are first converted
to their respective nucleosides, which are then
phosphorylated to nucleotides (Figure 9.8).
Neither hypoxanthine nor guanine is metabolized
by either parasite. Thus, both T. vaginalis
and E. histolytica lack PRT enzymes. Enzyme
measurements in lysates confirm the results
of the radiolabeling experiments. T. vaginalis,
like G. lamblia, also lacks RR activity, and the
parasite, therefore, is a deoxynucleoside auxotroph
(Figure 9.8). A deoxynucleoside-specific
NP activity that does not recognize ribonucleosides
has been detected in T. vaginalis.
Although it is conjectured that E. histolytica
has an RR activity, the evidence is indirect. The
parasite is sensitive to growth inhibition by
hydroxyurea, a free radical scavenger that
inhibits RR in other systems. Whether RR is the
cellular target for hydroxyurea is unclear.
Helminths
Purine metabolism in worms has been investigated
in only a few parasites and in a relatively
cursory fashion. Like protozoan parasites,
Schistosoma mansoni adults and schistosomules
lack the capacity to synthesize purine
nucleotides de novo. The schistosomules can
salvage hypoxanthine, guanine, adenine and
their corresponding nucleosides, but not xanthine.
Interconversion among the adenine
and guanine nucleotide pools is minimal. The
schistosomules express AP and APRT activities,
which are likely routes for adenosine/adenine
metabolism. They also express low, but
sufficient, amounts of AK to initiate tubercidin
metabolism and toxicity. In contrast to the
schistosomules, adult worms have high levels
of AK and ADA activities, in addition to the AP/
APRT routes of salvage found in the schistosomules.
The S. mansoni HGPRT gene has been
cloned, and the protein purified, characterized
biochemically, and its three-dimensional
structure determined. The enzyme is similar
to the human HGPRT in structure and substrate
specificity. There is no separate XPRT, although
GD activity, which produces xanthine, is high.
Purine metabolism in nematodes and cestodes
is largely uncharted. The dog heart
worm, Dirofilaria immitis, and the cat and primate
filarial worm, Brugia pahangi, both lack
the de novo pathway, but not much else is
known. Ascaris lumbricoides possesses a number
of purine salvage enzymes and the capacity
to break down AMP, adenine, xanthine, urate,
and allantoin to urea and ammonia, a purine
BIOCHEMISTRY AND CELL BIOLOGY: PROTOZOA