concentrations of intracellular binding protein shift
the local equilibrium so that the vitamins are
unloaded from the transport protein and onloaded to
the intracellular binding protein. In this way,
protein binding also results in directed delivery of
these vitamins. The other fat-soluble vitamins are
transported in lipoproteins and are widely distributed
in cell membranes and body fat.
When the dietary intake of a trace mineral or
vitamin exceeds the body needs for the
micronutrient, the excess may be accumulated in the
active tissues as reserve supplies or it may be distrib-
uted to storage sites. Iron is accumulated both in
marrow cells as a supply reserve and in hepatocytes
as a store. Additionally, the iron from senescent red
cells is recovered by and stored in fixed tissue
macrophages of the marrow and spleen. At all these
sites, the surplus iron complexes with the intracellu-
lar binding protein apoferritin. The iron-apoferritin
complex is referred to as ferritin. Iodine is the only
other trace mineral that the body accumulates. It is
taken up into thyroid follicles where it exists as a
supply reserve covalently bound to thyroglobulin.
For both iron and iodine it is important for the cell
to maintain the mineral complexed or bound to
protein to protect against cellular toxicity from the
free ionic forms. Cobalamin and folate accumulate
in the marrow and in hepatocytes primarily bound to
cytosolic and mitochondrial enzymes. In addition,
folate is retained in the cell as free folylpolyglumates
which, unlike folylmonoglumate, do not diffuse out
of the cell, owing to the highly charged polyglumate
tail. Retinol is stored in the liver in specialized
accessory cells called stellate cells (also called Ito
cells). The other fat-soluble vitamins are also stored
in the liver but in the hepatocytes. Tocopherol,
menaquinone and phylloquinone are present in
adipose tissue but this is a site of slow turnover
which may not function as an available store.
Vitamins are lost by urinary excretion and by
catabolism within the active tissues. Trace minerals
are lost by urinary excretion, by desquamation of
skin and intestinal cells, and by insensible fluid
losses. Only the unbound plasma species are avail-
able for urinary excretion.
Circulating forms of micronutrients
Trace minerals and vitamins circulate not only in
their transport forms but may also be present in their
supply and storage forms which enter the plasma as
a result of cellular turnover in the active tissues and
in the storage tissues, respectively. Trace minerals
may also be incorporated into plasma constituents
(product forms) secreted into the plasma from their
sites of synthesis.
The plasma concentration of the storage form of
a trace substance can be used as a marker of the
body stores of the substance. The plasma concentra-
tion of the storage form depends upon the rate at
which the storage form enters the plasma. That
entry rate is the product of the rate of turnover of
storage cells and the amount of substance stored in
each cell. In the absence of other perturbing influ-
ences, the rate of cell turnover among storage cells
is constant. The plasma entry rate then depends only
upon the amount of the storage form liberated per
dead storage cell which is, in turn, determined by
the tissue stores of the substance. Thus, the plasma
concentration of the storage form is proportional to
the body stores of the substance. When the rate of
cell turnover in the storage tissue is increased, as
occurs with injury or in neoplastic tissue, the release
of the storage form is increased and its plasma
concentration will be elevated, thereby compromis-
ing the relationship between the concentration and
the size of the body stores.
In a similar fashion, the plasma concentration of
the supply form of a micronutrient can be used as a
marker of the supply of the micronutrient in the
active tissues. Additionally, a plasma product form
of a micronutrient substance can be used as a marker
of the supply of the trace substance in the tissue
secreting the product. A reduced supply of micronu-
trient results in diminution in the rate of synthesis
and secretion of the product form. Because the
plasma concentration of the product form depends
upon its rate of secretion, the magnitude of the
deficiency in the active tissue supply will be
reflected in the product form concentration. Of
course, other influences upon the rate of secretion of
the product form can cause alterations in its plasma
concentration that can be confused with or can
obscure changes due to decreased micronutrient
supply.
The plasma concentration of the transport form
of a trace substance depends upon the rate of entry
of the form into the plasma from the diet and from
body stores and its rate of egress from the plasma
into sites of utilization and back into body stores. If
the major source of the transport form is the body
stores, the concentration of the transport form will
generally parallel those stores. If the transport form
Nutritional Status
8-3
