Chapter 5. Digestion and Absorption of Minerals
K
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.
O
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 mineral’s 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 mineral’s 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
Blood
Apical (lumen) side
Na+
Na+
Cl-
Glucose
Glucose cotransporter
Amino acids
Amino acid transporter
Na+
H+
Na+/H+ antitporter
H+
Carbonic anhydrase
H+ + HCO3-
H2CO3
CO2
CO2
H2O
Cl-
HCO3Anion antiporter
Intestinal Enterocyte
Figure 5.1. Absorption of Na+ and Cl- across the intestine.
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 sodium-glucose 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.
-Vit D
- Vit D + 1,25-(OH)2-D3
100
100
Calcium
Absorbed
Non-Saturable
50
50
Saturable
0
0
0
100
200
Dietary Calcium
0
100
200
Dietary Calcium
Figure 5.2. Absorption of Calcium in the Duodenum of the Rat
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 post-transcription, 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.
Duodenum
Jejunum
Ileum
100
Non-saturable
50
Saturable
0
Saturable
0
0
100
200
0
0
100
200
0
100
200
Calcium Instilled, mM
Figure 5.3. Uptake of Calcium in Different Regions of the Intestine. Only the
ileum of the intestine is incapable of absorbing calcium in a regulated 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 (diffusiondriven) 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.
7
3.2% Ca, 0.8% P
6
0.9% Ca, 0.8% P
(normal)
5
Daily weight 4
gain (g)
3
2.5% Ca, 1.7% P
2
1
0
0
30
60
120 180 240 360 600 1200
Log of Dietary Mg (mg/100g)
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 lipid-rich 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 multi-valence 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 zinc-binding 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.
Lumen
CRIP
Rapid
Export
Zn
Zn
Zn
Zip4
Exchange
Metallothionein
Storage
Figure 5.6. Intracelluar zinc storage and transport.
CRIP (cysteine-rich intestinal protein)
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 C-terminal 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.