Chapter 5.

Digestion and Absorption of Minerals

ey :

Minerals present in food are part of a food matrix consisting mainly of

protein, complex carbohydrate and fat. Digestion is targeted at the matrix
structure, using hydrolytic enzymes to degrade and eventually liberate the
minerals from there captive surrounding. Macrominerals tend not to be bound
firmly in such complexes. In contrast, microminerals are more firmly fixed to
the matrix molecules and hence complete release is not in the offing. The
acidity of the stomach aids in both releasing the mineral from the matrix and
rendering it into a free and soluble form. Very little absorption, however, takes
place in gastric cells and hence the bulk of mineral absorption must await
entrance into the duodenum and mucosa beyond. There is a danger, however.
Entrance into the duodenum is accompanied by a drastic rise in pH, from an
acidic environment of gastric juice to the modest alkaline environment of the
duodenum. As noted in Chapter 2, an alkaline environment works against
solubility of many minerals and thus without the assistance of solubilizing
factors, many microminerals, and to some extent macrominerals tend not to be
absorbed.

DIGESTION
1. General Principles
The purpose of digestion is to render large composite macromolecules in
food into smaller more manageable components. This is achieved by a group
of hydrolase enzymes that are present through out the digestive tract and
within the membranes of absorbing cells. There are three distinct stages in the
digestion process, (1) salivary, which involves amylases secreted from the
salivary gland that breakdown glycogen and starch, , (2) gastric, which
concerns mainly pepsin secreted from chief cells that attack proteins (3)
mucosal, which involves both trypsin and chymotrypsin synthesized in the
pancreas and released into the duodenum to digest proteins. The second
phase of mucosal digestion uses peptidase and glycosidase that are embedded
in the membranes of the absorbing mucosal cells as a final phase by attacking
smaller peptides and di-and trisaccharides allowing them to enter as individual
amino acids and monosaccharides. Incidental to the action of these enzymes
is the release of the minerals such as iron, calcium, magnesium that were in
the food matrix. Spared from the digestion are amino acids and
monosaccharides, which can function in aiding the solubility and absorbability
of minerals.

ABSORPTION

I. General Principles
Postdigestion processes in the absorbing region of the intestine expose
minerals to a whole new environment of cells. Cells that line the intestine are
basically columnar epithelialcells with a pronounced microvillus lining their
exposed surface. Passage into the system confronts first the microvilli on the
outer boundary which form the absorbing surface supported by a membrane
that regulates movement into the cytoplasmic interior. Absorption is not
complete until the passage from the entry portal release from the opposing
surface is completed. Once thought to be a simple oozing through a mucosal
barrier, minerals absorption in the small intestine is now regarded as a highly
complex, energy-driven process tuned to the prevailing mineral content within
the system. Understandably absorption is a key site for mineral-mineral
interactions, and mineral sequestering, which potentially can disrupt the
orderly flow of minerals into the system. It is at the intestinal stage that the
system is at its highest level of vigilance against excessive mineral intake. To
approach absorption we key on membrane transport systems that pass
minerals across intestinal cells. We also key on the energy factors driving
these processes as well as their regulation and mechanism. Intestinal
absorption and bioavailability are at the heart of nutritional need and both
decide the difference between a healthy outcome or a not- so-healthy mineral
deficiency.

bjectives:

1. To characterize specific intestinal transport systems for minerals,

2. To gain insight into the mechanism for moving a mineral across the
barrier,
3. To learn what regulates the action of membrane transporters,
4. To identify factors in the diet that impede or aid the absorption of
specific minerals.
Guiding Principles of Absorption
Control of a minerals homeostasis within the system begins at the
absorption stage.
Below is a list of 6 key factors that must be addressed when deciding the
absorption of minerals. All of these factors have been determined by careful
studies of the absorption process relative to particular minerals.
1) Absorption can be highly selective for the form of the mineral,
2) Absorption of a particular mineral is greater when there is a nutrition
need for that
mineral,
3) Most dietary factors that impede a minerals utilization by the system
exert their
action at the absorption phase,

4) Metal antagonism can arise when two minerals compete for a

common portal,
5) Vitamins and hormones that facilitate the passage of specific minerals
(Ca2+, HPO4=,
Mg2+, Fe2+) generally work at the level of intestinal
absorption,
6) For many minerals, especially microminerals, absorption depends on
the movement of vesicles that cycle between the luminal surface membranes
and an internal compartment.
2. Absorption of Macrominerals
1) Sodium and Chloride
Macrominerals such as Na+ and Cl- have the advantage of occurring in
bulk amounts in the diet and are present in foods mainly as unattached ions.
Consequently, digestion aimed at liberating sodium and chloride from the food
matrix is not a major concern. A second point to consider is that sodium ions
being present in bulk amounts are a major force driving other components
inward via a co-transport mechanism. Figure 5.1 shows transporters for
glucose and amino acids use the energy from sodium gradients to drive
glucose and amino acids into the mucosal cells. A third uses an ATP-driven
hydrolysis of water to

create and then drive the exchange of Na+ for H+ thus maintaining
electroneutrality. The glucose- and amino acid cotransporters aptly
demonstrate the power of simple diffusion in intestinal absorption, which
accounts for about 50% of the Na+ taken in through the intestine;
electroneutral cotransport accounts for only about 20%. Both the sodiumglucose and the sodium-amino acid transporter systems are on the apical

surface of the enterocyte and show interdependence to one another. This

illustrates an important nutritional point, that glucose and amino acids
themselves are powerless to penetrate the enterocyte without sodium ions
providing the energy.
In contract to Na+, the absorption of Cl- relies on an exchange reaction
replacing bicarbonate anion with Cl- (Fig. 5.1). The bicarbonate (HCO3-) is a
synthesized from CO2 via the enzyme carbonic anhydrase. HCO3- arises by
dissociating a proton from carbonic acid (H2CO3) which positions the H+ to
partake in the Na+/H+ exchange.
In general the amount of Na+ and Cl- taken into the organism is not
regulated at the intestinal stage. Maintaining homeostasis within the system,
therefore, shifts to the kidney and to a lesser extent, biliary secretions and
sweat glands. The co-transport with glucose renders carbohydrate- rich diets
competent to raise the sodium intake, which makes organic components in the
food source a deciding factor in the amount of sodium taken into the system.
2) Potassium
Potassium is the most abundant cation in the body with the body load
estimated at between 3000-4000 millimoles. Nearly 98% of this is within cells.
It is no wonder, therefore, that there is an exceptional need for potassium in
the diet and absorption systems for potassium operate at nearly 100%
efficiency with both proximal and distal parts of the intestine taking an active
part. In contrast to sodium, there is no glucose or amino acid co-transport with
potassium. Rather, potassium relies on conductance channels across the
membrane with energy provided by a H+/K+-ATPase similar to the H+/Na+
mentioned earlier, but selective for potassium ions. Potassium is also absorbed
through a K+/Cl- cotransporter. As with sodium, potassium absorption is
unregulated at the intestinal stage and requires the kidney to maintain
homeostasis. Indeed, it has been estimated that the kidney will eliminate the
daily dietary load of potassium in a 24 hour period.

Figure 5.2. Potassium channel in the membrane. The V-shaped funnel has the
cytoplasmic side facing down. A channel is formed by the interaction of 4
proteins with identical subunits.

3) Calcium
In the realm of the divalent cation transport, there is an increasing
propensity for dietary factors to be more influential in the absorption process.
One reason is because divalent as opposed to monovalent cations form stable
complexes with proteins and other factors in the diet. Thus, divalent cations
such as Ca2+, Mg2+ do not share the same high absorption efficiency as
monovalent ions. Researchers have attempted to elucidate the mechanism of
calcium absorption across the intestine with this thought in mind. Magnesium
predictably has some overlap with calcium. Calcium absorption, however,
unlike magnesium is clearly dependent on vitamin D, specifically the 1,25
dihydroxy derivative of the vitamin.
Calcium crosses the intestine by two major avenues; through the cell
barrier or around it. Through the cell (transcellular) accounts for most of the
calcium absorbed. Around the cell (paracellular) is mostly by diffusion and is
unregulated. Transcellular is a metabolically active,

Figure 5.3. A calcium channel protein in the membrane. The channel for calcium is formed by
a single polypeptide chain crossing the membrane in four different locations .

oxygen-dependent process that moves calcium against a concentration

gradient. Vitamin D is required for this system. Studies with intestinal

segments suggest that the proximal end of the intestine is most active in
transporting calcium. In the presence of 1,25 dihydroxy-D3 (the most active
form of vitamin D) calcium uptake is curvilinear with increasing dietary calcium
as seen in Figure 5.4. The response is suggestive of a saturable system,
suggesting a carrier. Without the vitamin, calcium still enters the cell but the
uptake is by diffusion and is no longer regulated.
In Figure 5.3, its can be seen that other than the duodenum, the jejunem is the
only other segment of the intestine that shows saturable uptake in the
presence of vitamin D. One may surmise that it is within these regions most of
the calcium is absorbed.
1) Calbindin as a mediator of calcium uptake
It could be argued from kinetic analysis that diffusion alone cannot
account for the rapidity with which calcium ions move across the intestine.
Instead, the data imply the existence of a rapidly moving carrier facilitating the
transfer. Efforts to identify the carrier led to the discovery of a small, 9
kilodalton protein that appeared to be specific for calcium. The protein was
given the name calbindin. Biochemical studies have since identified two high
affinity binding sites for calcium in calbindin, showing that a modest calcium
input can still lead to major calcium incorporation. Calbindin concentration in
cells can be as high as 0.2-0.4 mM, which suffices to augment calcium
movement under conditions prevailing in cells. Moreover, it now appears that
the enhancement of calcium transport correlates strongly with the level of
calbindin in the transporting cell. Recently, 1,25-dihydroxy-D3 has been shown
to control the synthesis of calbindin at the level of transcription and posttranscription, thus suggesting that calbindin is the agent that makes possible
vitamin D-dependent calcium transport. Linking vitamin D with calbindin has
thus help explain how vitamin D controls calcium uptake. It should also be
noted that calbindin null mice (those unable to make the protein because of the
inactivation of the calbindin gene) do not lose the ability to transport calcium,
which suggests other calcium transporters are present. Moreover, calbindin is
also expressed in a variety of tissues including uterus, kidney, pituitary gland,
and bone and thus may be regulated by other factors in a tissue-specific
manner.

4) Magnesium and phosphate

On first impression one may consider the absorption of magnesium to
mimic calcium. Such is not the case, however. Isotopes of magnesium (28Mg2+)
tend to support the conclusion that the ileum and colon, not the jejunum, are
more active in absorption of this metal ion. Like calcium, however, magnesium
employs both active (energy-dependent) and passive (diffusion-driven)
transport. Active is characterized by saturation with increased intake.
Generally the response to magnesium is curvilinear, suggesting saturation at
the higher levels and diffusion at the lower. Diffusion, however, only accounts
for 7-10% of the magnesium taken in. This signals involvement of a mediated
factor that conducts the movement across the membrane. Unique to
magnesium that was not seen with either sodium or potassium was the
lowering of the fractional absorption with increasing amounts in the diet. For
example, raising dietary magnesium from 0.3 mmoles (7 mg) to 1.5 mmoles
(36 mg) lowered the fractional absorption from 65-75% to 11-14%. Unlike Na+
and K+, Mg2+ intake is clearly subject to regulation at the absorption stage.
One other striking observation is the apparent interference of Mg2+
absorption with Ca2+ and phosphorous (as phosphate). That observation infers
the two divalent cations may share a common carrier or entry portal and could
be subject to the same regulation. Long term studies, however, dismiss
interference between the two, but in the short term the fractional uptake of
Mg2+ is clearly influenced by the presence of Ca2+. Isolated segments of the
intestine suggest magnesium absorption is greatest in the ileum and not the
jejunum, which is the opposite of what is seen with calcium. As noted,
phosphorous seems to antagonize both calcium and magnesium (Fig. 5.4).
Evidence supporting commonality between magnesium and calcium is the

observation made with phosphorous. Phosphorous hinders absorption of both

magnesium and calcium. Conversely, magnesium inversely affects phosphate
and to a lesser extent absorption of magnesium.

Figure 5.6. Uptake of Calcium in the Presence of Magnesium and Phosphorous. Guinea pigs were
fed increasing amounts of magnesium in diets that were fixed in calcium and/or phosphorous. Daily
weight gain was determined for each amount.

It is hard to conclude that all three minerals vie for a common carrier, certainly
not an anion vying for a cation carrier or entry portal. The last argument for
magnesium and calcium having their own unique systems of entry comes with
the role of vitamin D on the two. Although there is some disagreement among
laboratories, the overwhelming opinion appears to be that neither vitamin D
nor any of its metabolites at physiological doses influence the 3.

MICROMINERAL ABSORPTION
Microminerals display a variety of transport systems for movement
across the intestine. Some recognize more then one mineral. All adapt to the
form of the mineral in the lumen and work closely with factors that allow
penetration on the apical surface and release on the basal surface of the
enterocyte. Because of the selectivity each micromineral must be discussed
separately.
IRON
Valance state and organic form are the two major determinants of iron
penetration into a mucosal cell. Organic iron in a food digest is present as
heme, a complex of iron with porphyrin and representing the most common
biochemical form of iron in the diet (Chapter 4). Inorganic iron, often referred
to as non-heme iron, is dependent on valence. As we noted in Chapter 2, iron
present as Fe2+ is more soluble that Fe3+ . The Fe2+ is generally the preferred
form for effective uptake, although oxygen in the water can readily oxidize Fe2+

to Fe3+, which then precipitates out as an insoluble polyhydroxy complex. A

further concern is that because of its redox activity, iron is a highly toxic and
can poison a system and through its peroxidant activity. This especially true for
free iron that can become localized on the membrane surface of cells in a lipidrich environment. These factors must be taken into account when considering
the mechanism for iron penetration across the intestine.
Heme iron is derived mostly from meat and blood proteins such as
cytochromes and hemoglobin. Iron in this form is basically soluble and stable,
which means it readily passes through the cell membrane as an intact complex.
A strongly acidic medium such as stomach acid can cause some of the bound
iron to dissociate from the porphyrin ring, but the bulk, however, stays intact.
Heme undergoes a quick efficient passage through the mucosa, possibly
involving no carrier of mediator and therefore is basically unregulated. These
observations form the basis for considering heme iron more bioavailable to the
organism.
More concern is directed at the passage of non-heme iron or so-called
inorganic or free iron. Because this form is insoluble at the pH of the intestine
and iron in this form has prooxidant properties, enterocytes release
gastroferrin, a mucous protein that coats the absorbing surface and villae of
the enterocyte. Gastroferrin retards the polymerization of the non-heme iron
keeping the ion in a quasi free singular form for easy passage into the cell at
the same time protecting the cell from wanton prooxidant activity.
Pathways of inorganic iron uptake
Depending of valence of the iron, there are two pathways for inorganic
iron uptake into intestinal cells.
1) The ferric pathway. This pathway is mediated by the protein
mobilferrin. Mobilferrin is localized in the cell membrane, more specifically in
the apical surface of the villae, where a majority of the protein appears to be
bound to the gastroferrin in vesicles near the surface. As the name implies,
mobilferrin is free to move through the cell with iron trapped within a vesicle.
By encapsulating the iron mobilferrin is capable of transcellular movement to
the exporting surface on the serosal side where it becomes anchored to
integrin, an all-purpose non-specific membrane protein that participates in
adhering non-membrane protein to cell surfaces. The complex is further
stabilized by HFE, a protein originally found in leucocytes and now speculated
to be essential for iron as well as zinc movement from enterocytes.
2) The ferrous pathway. Iron as Fe2+ is the more soluble form. The
ferrous pathway features a unique membrane transporter, DMT-1 (divalent
metal ion transporter) sometimes called DCT-1 (divalent cation transporter) and
formerly Nramp2. The transport is not specific for iron but instead can serve to
transport a variety of divalent cations. Movement is from the apical surface of

the villae to the basolateral surface. In the ferrous pathway transport can only
occur if the iron is in the Fe2+ form. For this reason Vitamin C is capable of
facilitating iron uptake by converting iron to the ferrous form (Fe2+) which is the
more soluble form. This explains why vitamin C, a strong reductant, tends to
enhance iron uptake. As a consequence, a large percentage of iron taken in is
able to pass into the mucosal cells. Once inside the mucosal enterocyte, the
iron is subject to being trapped by mucosal ferritin which further delays its
movement into the system and forms the basis for only a small fraction of the
iron taken in diet ever reaching the blood. The DMT-1 transporter for ferrous
iron also recognizes other ions in the 2+ form. The latter include Cu2+, Mn2+,
Zn2+ and perhaps some macrominerals (Ca2+, Mg2+). This multi-recognition
property of DMT-1 form the basis for competition between these metals and
forms the foundation of metal ion antagonism.
Export stage of iron absorption
Passage out of the cells is the final stage of iron transmembrane
movement. Mobileferrin mentioned earlier in the uptake is also a component in
the release of iron from the cells. The major protein conducting the release is
ferroportin. The importance of ferroportin was shown in mice that carried a
disabled ferroportin gene (referred to a knockout mutant). The mice were
capable of absorbing iron into enterocytes but could not excrete iron from the
cells implicating and establishing ferroportin as indispensable for the release of
absorbed iron into the system. The discovery of ferroportin draws parallels to
the discovery of a protein called IREG (iron-regulatory protein) and MPT1 (metal
ion transport protein), which may be one in the same protein. Ferroportin,
however, has been shown to have functional and regulatory links to hepcidin,
which many investigators in iron absorption have considered to be the master
regulatory protein controlling iron absorption at the export stage.
ZINC
Because zinc transporters need recognize only one valence state, Zn2+,
the passage of zinc into the cell would appear to be less complex than multivalence state ions. This is not the case. The omni presence of zinc in tissues
and fluids and cell compartments dictates a need for many different
transporters that operate in a variety of cellular environments. Such is the
case with the zinc family of transporters, referred to as Zip1-5. Of these, Zip4
is involved in zinc uptake from the intestinal lumen. Most of the other Zip
family zinc transporters are located in tissues other than the intestine. Most
are designed to operate in environments that vary widely from cell to cell. As
an example consider zinc in the brain cells as compared to the zinc in the
intestine works in the environment of synaptic vesicles. Neurons with these
vesicles in certain brain regions must handle high amounts of zinc and
therefore be less sensitive than transporters that work in an extremely sparse
zinc environment, which typifies the intestine after a meal. We will discuss the
other Zip transports in the chapter on Zinc.

Absorption Sites and Zip4 Transporter

The absorption of zinc is strongest in the upper intestine which includes
the duodenum and ileum. Lower rates occur in the stomach and large
intestine. Amino acids, dipeptides, and organic acids present in the lumen
tend to hasten absorption whereas slower rates occur when energy is deprived.
Entry into the enterocyte, like iron, is facilitated by mucous proteins and
carbohydrates secreted by the absorbing cells. As noted Zip4 is the major
player in zinc absorption. DMT-1 appears to play a less critical role for zinc
entry. The focus on the Zip4 protein and gene represented the outcome of
studies aimed at identifying the defective gene in a condition known as
acrodermitis enteropathica (AE). Patients with AE display all of the symptoms
of zinc deficiency, which include impaired growth, immune system dysfunction
and mental disorders. Fibroblasts from these patients are unable to absorb
zinc, which points to a zinc-binding protein as the factor. Of the various zincbinding proteins, most AE patients were found to have mutations in the gene
that coded for the Zip4 protein. Zip4 is located in the absorbing surface of the
cell or an internal compartment. With a diet deficient in zinc, Zip4 remains
mostly on the surface of the enterocyte. Low zinc impairs the inward
endocytosis of Zip4 and hence the protein remains strategically positioned to
absorb more zinc. In contrast, a high or normal zinc diet leaves most of the
Zip4 protein in an intracellular compartment out of contact with luminal surface
and in a position where absorbing zinc is prohibited. The movement of the Zip4
protein in AE patients cannot be controlled by zinc and hence these patients
are in a chronic zinc-deprived state.
Intracellular Movement
Movement of zinc through the enterocyte involves more than Zip family
proteins.
Based on the rate of passage, there appears to be at least two
pools of zinc in the enterocyte. One shows a rapid displacement of zinc
through the cell; the other a slower movement and a tendency to actively
exchange with endogenous zinc. The latter pool represents a more controlled
zinc uptake and may even be considered a stopgap response to high zinc influx
. The regulated path is controlled by the protein metallothionein. This small,
cysteine-rich protein binds and sequesters zinc (not unlike the ferritin with
iron). High zinc influx causes metallothionein levels to rise because zinc is a
transcription factor for inducing metallothionein synthesis. Blocking the
outflow path with a zinc-binding protein is seen as a response that protects the
system from absorbing potentially toxic levels of zinc. A second a protein
called CRIP (cysteine-rich intestinal protein) binds zinc when zinc input is low
and tends to be the factor that gives rapid throughput. The interaction of the
two is seen in Figure 5.6. Higher absorptive efficiency correlates with a higher
proportion of absorbed zinc bound to CRIP, which strengthen the case for CRIP
being the factor that allows rapid uptake. Lower efficiency is seen when zinc is
in excess or when the internal supply of zinc is adequate. Thus, the

competition between CRIP and metallothionein for zinc is tuned to the zinc
status of the individual and the diet and is regulated at the level when zinc
enters the intestinal cell.

COPPER
Copper once again reintroduces the importance of valence state in the
movement across the intestine. Only about half of the dietary copper enters
the system. The lower valence state (Cu+) is the state that is least soluble and
could account for most of this loss. Like iron, however, there is a special
transporter that recognizes only one valence state of the ion, the Cu+ ion.
Although it is likely that some Cu2+ enters the enterocyte via DCT1, Cu+ is form
taken in through the uptake channel protein, CTR1 (copper transporter 1).
CTR1 that drives intestinal copper transport is present in the membrane as a
trimer (three identical subunits) that extends through the bilayer. The trimeric
protein forms a hole in the membrane through which copper ions move inside.
How copper ion move through the channel is unknown, but since Cu+ behaves
more like a closed shell ion, the driving force is likely to be provided by the
membrane potential.
Working in conjunction with CTR1 is a reductase enzyme that converts
Cu2+ to Cu+ preparatory to being taken in by CTR1. Once inside the enterocyte
the Cu+ ion can be sequestered by metal-binding proteins which either transfer
the copper to other regions or store the copper as metallothionein-bound
copper.
ATP7A
The counter part to the zip4 protein for zinc is a membrane-bound copper
transporting protein designated ATP7A. ATP7A is a member of large family of
membrane proteins, which as a class use the energy of ATP hydrolysis to drive
ions into and out of cells. ATP7A is a membrane bound enzyme that localizes

in both the membrane surface as well as internal vesicle compartments, i.e., is

found in the membrane of movable vesicles. It is the primary factor exporting
copper from the cell as part of the cellular release mechanism. The discovery
of AT7A came to light with studies that probed the cause of Menkes disease in
children. Children with the disease, nearly always males, were unable to
absorb copper across the intestine and in so doing developed a severe copper
deficiency that proved fatal at about the third year post natal. The disease is
actually manifested in utero. A search for the factor led to the discovery of a
unique protein that had been described earlier in bacteria and was shown to be
involved in the preventing the bacteria from toxic exposure to copper. When
the gene for ATP7A, the human form, was isolated and sequence it bore an
amazing resemblance to the sequence of the bacterial protein. The research
culminated with the discovery that Menkes sufferers had a defect in the gene
for this protein. The lesion was found to be in the ATP binding site and in the
channel of the protein. More recent data has revealed that ATP7A gene is
subject to numerous mutations, most of which are harmless to function. Those
that are, however, tend to strike at specific sub-functions of the protein. For
example, mutations in the exons coding for the C-terminal region tend to inhibit
the protein from localizing to the export surface. Hence, the role of the Cterminal amino acids could clearly be linked to vesicle movement and docking.
Studies linking other regions of the protein to function continue today.

SELENIUM
Selenium in the diet is primarily present as selenocysteine and
selenomethionine. One can expect these seleno amino acids to use the same
carrier system that are for their sulfur counterparts. In addition, the system
can absorb inorganic selenium such as selenate and here the concern is with
the solubility.
SUMMARY

The varieties of minerals that are present in foods present no advantage

to the organism until they are freed from surrounding by digestion and
absorbed across the intestine into the system. Different minerals employ
different mechanisms for accessing the interior of the system, a fact that has
made it a necessity to treat each mineral in a novel way and call attention to
generalities only rarely when they emerge. The absorption of macro- and to a
greater extent micromineral is carefully regulated through adjustments in
absorption efficiency. Sodium absorption is coincidental to the absorption of
carbohydrates and amino acids. The energy for effecting movement is
provided by a diffusion-driven sodium gradient across the membrane as well as
ATP hydrolysis. Working to their advantage, macrominerals are highly soluble
in the environment of the lumen and move easily in the aqueous phase.
Solubility is only one consideration in rationalizing a need for a ligand. Because
they lack the quantity, microminerals rely on proteins to bring about
absorption. This is tantamount to saying that diffusion-controlled mechanisms
do not apply to the intestinal absorption of microminerals and shifts emphasis
to the role of membrane factors that represent portals for entrance. These
portals work in conjunction with energy driven movement provided by ATP. The
release phase of absorption is critical to bringing the absorbed components into
the system. Here, the concern is regulation and control of entry to safe guards
against excess uptake.