trans

200 PURINES AND PYRIMIDINES
provide overviews of the key pathways in the
more prominent model parasites and emphasize
the new knowledge that has accumulated
over the last decade. The reader is referred to
the selected readings given at the end of this
chapter for more background information.
Because of their lengthy names and the frequency
by which they will be referred in this
review, all enzymes will be designated in the
text by their acronyms, listed in Table 9.1. When
referring to an enzyme from a specific species,
the abbreviated enzyme will be preceded
by initials describing the genus and species,
e.g. Plasmodium falciparum hypoxanthineguanine-xanthine
phosphoribosyltransferase
will be PfHGXPRT.
TRANSPORT SYSTEMS
The salvage of exogenous purines and pyrimidines
is initiated by the translocation of either
the nucleoside or nucleobase across a single
or, in the case of intracellular parasites, multiple
membranes. Since nucleosides and nucleobases
are hydrophilic and consequently cannot
diffuse across the lipid bilayer, parasites have
devised specialized translocation systems,
each uniquely adapted to their hosts’ environments.
Until recently, most of our knowledge
derived about transporters has arisen from
observations on transport into intact parasites
or parasitized host cells. However, molecular
genetic tools and the burgeoning parasite
genome databases have led to the identification
and functional characterization of a
number of parasite translocation proteins. Thus
far, all of the parasite genes identified appear
to belong to a family of transporters, termed
the Equilibrative Nucleoside Transporters
(ENTs), after their mammalian homologs.
These transporters are distinguished by an
overall similarity in predicted topology (11
transmembrane domains) and possess a number
of conserved or signature residues, located
primarily within predicted transmembrane
domains (Figure 9.1). Many specialized mammalian
cell types, such as kidney and intestine,
also contain another class of nucleoside transporter
that couples nucleoside uptake to the
cellular Na or H gradient. These Concentrative
Nucleoside Transporters, CNTs) have yet
FIGURE 9.1
Predicted topology and conserved residues of the equilibrative nucleoside transporter (ENT) family.
BIOCHEMISTRY AND CELL BIOLOGY