retinol, retinol-binding protein pair, the two-ligand,
two-binding protein complex is too large to be
filtered at the glomerulus (Blomhoff
et al.
1990).
Binding proteins which serve a delivery function
render the plasma constituents bound to them avail-
able for uptake in certain tissues, and unavailable to
others. The differential bioavailability of bound
constituents is achieved in two ways. First, protein
binding may render a plasma constituent available
only to tissues with specific receptors for the
constituent. An example is (unconjugated) bilirubin
which, when unbound, has a high lipophilicity and
can readily diffuse across plasma membranes and
nonspecifically enter tissue cells. When bound to
albumin, bilirubin is excluded from tissue cells
except the hepatocytes which appear to have a
plasma membrane receptor for bilirubin (Muller-
Eberhard and Nikkilä 1989). Second, protein
binding may make a plasma constituent available
only to tissues with specific receptors for the binding
protein. Iron bound to transferrin, for example, is
selectively delivered to red cell precursors because
they have a high density of transferrin receptors on
their surface. Iron is also available to liver and
placenta as these tissues also express cell-surface
transferrin receptors in large numbers but iron
uptake in other tissues, which have much smaller
numbers of receptors, is meager (Huebers and Finch
1987).
Another possible but unproven function for
plasma protein binding is to "buffer" acute changes
in the extracellular concentration of a ligand: if the
protein-bound form of the ligand is not bioactive,
bound ligand could serve as a ready source of the
ligand if the bioactive unbound form were acutely
depleted and unoccupied binding sites could serve as
a ready sink for the ligand in the event of an acute
plasma excess of ligand. This function is usually
presented as a mechanism to protect the organism
from the detrimental effects that would otherwise
attend a sudden change in a substance's extracellular
concentration. Calcium and magnesium are likely
candidates for such protective buffering. Acute
changes in the extracellular concentration of the free
form of either cation can have catastrophic effects
upon cardiac and nervous system function. Buffer-
ing could also be a mechanism to maintain more
stable plasma concentrations of substances otherwise
Organ Function
7-12
Table 7.1
Transport Functions of Protein Binding
Constituent
Transport Function Specific Binding Protein
Vehicle
Storage
Delivery
oxygen
yes
hemoglobin
bilirubin
yes
yes
albumin
hemoglobin
yes
yes
haptoglobin
heme
yes
yes
hemopexin
iron
yes
yes
yes
transferrin
copper
yes
albumin
90% of plasma copper is contained in ceruloplasmin
zinc
yes
albumin
30% of plasma zinc is contained in
α
2
-macroglobulin
calcium
albumin
magnesium
albumin
retinol
yes
yes
retinol-binding globulin
cobalamin
yes
transcobalamin II
cholecalciferol
yes
possible
vitamin D-binding globulin
thyroxine
possible
thyroxine-binding globulin, prealbumin
triiodothyronine
possible
thyroxine-binding globulin, prealbumin
aldosterone
possible
cortisol
possible
cortisol-binding globulin
testosterone
possible
sex hormone-binding globulin
estradiol
possible
sex hormone binding globulin
