considerable variation exists in the amino
acid requirements of these cells and in the
complement of ‘transport systems’ that are
expressed to meet these requirements.
Transport systems (or activities) generally
are defined as that protein which recog-
nizes and transfers a selective group of sub-
strates across cellular membranes, whether
acting singly or in combination with other
proteins. Although best characterized in
the plasma membranes of non-polarized
cells (e.g. muscle and endothelial), and the
apical and basolateral membranes of
polarized epithelial cells (e.g. enterocytes
and hepatocytes), free (amino acid) and
peptide-bound (peptide) amino acid trans-
port systems also mediate the passage
of substrates across the membranes of
cell organelles (lysosomes, mitochondria,
nucleus, etc.).
Transport proteins allow the cell (or
organelle) selectively to bind and acquire
compounds from a milieu of other sub-
strates. The physiological importance of
transporters is usually discussed in terms
of their relative ability to recognize and
bind a substrate molecule (affinity), and the
amount and rate of substrate translocation
through the membranes (capacity/velocity).
Typically, transport systems that demon-
strate relatively low affinities for substrates
have large capacities for transport, whereas
those that display high affinities have
low capacities. The general process of
transporter-mediated passage through
membranes, however, is the same for all
transporters: (i) the substrate(s) binds to the
recognition domain of the transporter; (ii)
the substrate(s) is translocated through the
membrane interior into the cell interior
(cytoplasm); (iii) the substrate(s) dissociates
into the cytosol; and (iv) the substrate-
binding and translocation domain(s) of the
transporter is reoriented for future sub-
strate binding.
Eventually, the process of transport
requires the expenditure of respiration
energy. The coupling of energy to drive
transporter function typically is described
as direct (primary) or indirect (secondary
and tertiary) processes. Primary trans-
porters are energized by the direct transfer
of chemical energy stored in high-energy
phosphate bonds of ATP (adenosine 5′-
triphosphate), as ATP is hydrolysed to ADP
and inorganic phosphorus. In contrast,
secondary transporter function is not
coupled directly to ATP hydrolysis.
Instead, secondary transport systems derive
the energy to translocate substrates across
membranes by harnessing the differences in
the transmembrane electrical and chemical
gradients of substrates and (sometimes) co-
transported ions (Na+, K+, Cland H+). In
mammals, amino acid and peptide trans-
port occurs by indirect processes. For
example, Na+-dependent amino acid trans-
port systems are secondary transporters
that energize substrate translocation by
coupling the transfer of amino acids to the
large extracellular-to-intracellular Na+(e.g.
systems A, ASC and B) and Cl(systems
IMINO and GLY) gradients (Table 1.1). The
cell then pays for the ‘free’ ride of the
solutes down their electrochemical
gradients by expending ATP to fuel the
function of primary transporters (Na+/K+
ATPase and H+ATPase), which re-establish
the extracellular-to-intracellular concentra-
tions of the co-transported driving ions. One
amino acid transport system, system XAG,
uses both the extracellular-to-intracellular
Na+ gradient and the intracellular-to-
extracellular K+ gradients to energize the
transport of anionic amino acids.
Tertiary systems also utilize the energy
derived from the electrochemical gradient
of a co-transported ion(s), but, in essence,
exchange the driving ion for another ion
that is a substrate for a primary transporter.
For example, H+ ions are co-transported
with small peptides across the apical
membranes of enterocytes and released
into the cytoplasm by the H+/peptide
co-transporter (Table 1.2). The H+ then
is pumped out of the cell by the
apical membrane-bound Na+/H+exchanger
(driven by the extracellular-to-intracellular
Na+ gradient), thereby re-establishing
the extracellular-to-intracellular H+gradi-
ent. The extracellular-to-intracellular Na+
gradient is then re-established by the baso-
lateral membrane-bound Na+/K+ ATPase.
Hence, the H+/peptide co-transporter is a4 J.C. Matthews