Which transport mechanism is functioning in the intestinal cells

Endocrine cells secrete cholecystokinin and secretin. Their secretions are primarily regulated by chyme: the larger the amount of chyme present, the greater the secretions [ 11 ]. Most of these proteins cannot be absorbed by human body in their predigested state and must be converted into amino acids prior to absorption [ 13 ].

Digestion describes the process by which complex dietary substances are converted into simple forms that can be absorbed by the body. Protein digestion starts in stomach and finishes in the intestine. Three enzymes are important for protein digestion: pepsin, trypsin, and chymotrypsin [ 14 ]. The acidic environment in stomach denatures proteins and makes them available for proteolytic digestion. Pepsin is the major proteolytic enzyme in stomach, where it converts large proteins into smaller peptides.

The partially digested peptides enter small intestine, where they are further degraded by activated trypsin and chymotrypsin. Trypsin and chymotrypsin are secreted by pancreas as inactive forms and converted into active forms when secreted into small intestine [ 14 ]. Proteins digestion can be further enhanced by proteases, such as aminopeptidase N.

Aminopeptidases can digest proteins from the amino terminus and form single amino acids or di- and tripeptides [ 15 ]. Absorption of amino acids is mainly carried out by IECs through active transport [ 16 ]. These IECs are highly polarized, with the apical plasma membrane facing the intestinal lumen. Because there are different types of transporters localized in either apical or basolateral membranes, IECs can transport substances in one direction across the epithelium. There are more than 7 types of amino acids transporters in the apical surface of IECs [ 17 , 18 ].

At least 5 amino acid transporters are present at the serosal basolateral surface, which can transport amino acids out of the cells and into interstitial fluid [ 17 ] Figure 2.

The amino acids can then enter blood vessels for circulation. The undigested and unabsorbed substances enter the large intestine. The maintenance and growth of intestine is driven by the amount of luminal nutrients. High nutrient content causes increases in the cell number, villus length, and crypt depth [ 13 , 19 , 20 ].

In addition, the type of nutrients appears to contribute to alterations in the morphology and functions of IECs. High-protein diet was found to upregulate the expression of genes related to cell proliferation and chemical barrier function in rat colon [ 23 ]. This study demonstrated that high-protein diet increased the amount of undigested peptides entering the large intestine, modified the gut microbiota composition, and increased protein fermentation by bacteria, resulting in the production of numerous amino acid derived metabolites [ 23 ].

It was also found that treatment with amino acid solution 1. The treatment increased the proliferation markers e. The results demonstrated that the better absorption of electrolytes and nutrients could be, at least partially, attributed to an increased villus height induced by amino acid solution, and that the extracellular signal-regulated kinase ERK pathway in IECs was activated by the amino acid solution [ 24 ].

Oral supplementation of L-glutamine 0. In cultured intestinal porcine epithelial cells IPEC-1 , L-arginine stimulated the proliferation rate and attenuated the lipopolysaccharide- LPS- induced cell death [ 26 ].

IECs are tightly bound together in a monolayer by intercellular junctional complexes. These cell-cell connections allow the epithelium to form a barrier which separates the extracellular fluid at the luminal side of the cell from fluid at the serosal side and also prevents microbial invasion of interstitial tissues [ 27 ].

Tight junctions are a primary determinant of intestinal epithelial barrier properties and functions. Tight junctions prevent the direct diffusion of small molecules from intestinal lumen into the interstitial spaces and then into the blood vessels [ 28 ]. Disruption of tight junction structures by specific protein mutations or by aberrant signaling can be both the cause and effect of diseases [ 27 ].

In recent years, studies have established the important roles of glutamine in regulating the functions of tight junction proteins Figure 2. In human Caco-2 cells, a classic model for studying gut barrier function, it was found that glutamine deprivation or inhibition of glutamine synthetase significantly decreased the transepithelial resistance and reduced the expression of tight junction proteins.

Glutamine addition rescued the phenotype of barrier dysfunction [ 29 ]. Other junctional proteins such as ZO-1, occludin, and claudins have been reported as essential effectors of perijunctional actomyosin ring-mediated tight junction regulation [ 31 ]. In a piglet weaning-related gastrointestinal infection model, glutamine supplementation 4. Upon exposure to E. The study showed that glutamine supplementation was beneficial in mitigating the severity of infection, probably by reducing the mucosal cytokine responses and by preserving the intestinal barrier function [ 32 ].

Oral glutamine supplementation in an intestinal ischemia-reperfusion IR injury rats had significant increases in jejunal and ileal bowel and mucosal weight and villus height and crypt depth compared to IR-nontreated rats [ 33 ]. Deficiency in dietary glutamine has been reported to impair cell signaling and result in intestinal atrophy in both piglets and infants [ 35 ].

L-Arginine supplementation at a dose of 0. In an inflammatory bowel disease IBD mouse model, L-arginine supplementation suppressed the dextran sulfate sodium- DSS- induced intestinal mucosal injury and improved IBD clinical parameters e.

Dietary L-arginine supplementation also reduced the methotrexate-induced intestinal mucosal injury and improved intestinal recovery following injury in rats [ 38 ]. In ovo feeding of L-arginine has been reported to improve the development and barrier functions of small intestine of posthatch broilers, which was attributed to the activation of the mTOR pathway [ 39 ]. IECs play important roles in protecting the human body from microbial infections.

The intestines contain the largest number of immune cells in the body [ 40 ] and are continually exposed to a wide range of antigens and potential immune stimuli [ 27 ]. IECs can sense and respond to microbial stimulations to reinforce their barrier function and to participate in the coordination of appropriate immune responses, ranging from tolerance to antipathogen immunity. Because IECs function as a barrier between the intestinal microbiota and the host, they are important to the maintenance of the symbiotic relationship between gut microbiota and the host by constructing mucosal barriers, secreting immunological mediators, and delivering bacterial antigens.

Inflammasome expressed by IEC plays important roles in mucosal immune defense and inflammation [ 41 ]. Dysfunction of intestinal epithelium can cause diseases, and some diseases cause the abnormalities in intestinal epithelium, which could worsen the complications. The majority of immunological processes occurs in the mucosa [ 42 ]. The B cells usually dominate in the germinal centers of follicles and T cells scatter between follicles. Abnormalities in B cell functions can cause the development of autoimmunity [ 43 ].

B-1 cells produce most of the circulating natural antibodies. They can differentiate into immunoglobulin M- IgM- or IgA-secreting cells and affect tissue homeostasis and the maintenance of a symbiotic mucosal microbiota through BCR dependent and independent means [ 43 ].

The absence of IgA-producing B-1 cells in the intestines might increase the risk of food allergies [ 44 ]. Regulatory T cells Tregs are a subpopulation of T cells. They function to suppress dysregulated immune responses of other immune cells to maintain intestinal homeostasis [ 45 ].

Adequate nutrition is essential to the development and maintenance of the immune system. Extensive studies have shed light on the homeostatic regulation of amino acids in intestinal immunity. It was found that glutamine reduced the proinflammatory IL-6 and IL-8 production in intestinal biopsies, and enhanced anti-inflammatory IL level in the gut [ 46 ].

IL is mainly produced by leukocytes e. IL plays important roles in the maintenance of intestinal mucosal homeostasis and in the suppression of proinflammatory responses of innate and adaptive immune cells [ 47 ].

The results suggested that a decrease or loss of Bregs function exacerbated intestinal inflammation [ 48 ]. Amino acids have been shown to affect the development, maturation, and functions of B cells and T cells in the intestine.

Cobbold and colleagues found that depletion of the essential amino acid s inhibited the activation and proliferation of T cells and mTOR signaling in dendritic cells [ 52 ]. Glutamine has been found to be required for T cell activation. Depletion of glutamine blocked the proliferation and cytokine secretion of T cells. Ikeda and colleagues found that branched-chain amino acids BCAA, e.

Oral supplementation of L-arginine has been shown to improve the intestinal immune function and reduce bacterial and endotoxin translocation in experimental severe acute pancreatitis rats [ 55 ]. These findings may help understand the beneficial effect of glutamine on reducing morbidity and gut permeability in patients with multiorgan system trauma [ 56 ]. In a rat model of puncture-style brain trauma, glutamine administration reduced the gut damage and decreased intestinal NF- B activity and intestinal proinflammatory cytokines expression [ 57 ].

Oral and parenteral feeding studies have demonstrated that, in addition to the total protein intake, the availability of specific dietary amino acids particularly glutamine, glutamate, and arginine is also essential to optimizing the immune functions of intestine [ 42 ].

Deficiencies in amino acids such as tryptophan, arginine, glutamine, and cysteine can reduce immune cells activation [ 58 ]. These amino acids have been shown to play unique roles in maintaining the integrity, growth, and function of the intestine, in normalizing inflammatory cytokines secretion, in improving T-lymphocyte numbers, specific T cell functions, and the secretion of IgA [ 59 ].

Studies in mice have demonstrated that dietary amino acids stimulation regulates the homeostasis of macrophages in the small intestine. For instance, when mice were given total parenteral nutrition, which deprived the animals of enteral nutrients, there was a significant decrease in ILproducing macrophages e. The production of IL in small intestine is dependent on both diet and microbiota. These data demonstrated a strong association between amino acid deprivation and the impaired replenishment of intestinal immunity function; a prolonged protein amino acids deficiency impairs critical immune functions [ 61 ].

L-arginine has been shown to be involved in protein synthesis and in the regulation of many essential cellular functions including immune response, hormone secretion, and wound healing [ 62 ].

L-arginine 0. L-arginine and its metabolite ornithine promote colonic epithelial wound repair by enhancing cell proliferation and collagen deposition through activation of mTOR signaling pathway [ 64 ].

Dietary glycine and L-glutamine supplementation has been shown to protect the colonic wall of irradiated rats [ 65 , 66 ]. Gel images shown here were cropped to show specific bands of expected size representing glucose transporters.

Ghrelin was also unable to upregulate the expression of intestinal sglt2 in the presence of H89 in the culture media Fig. However, the ghrelin-induced upregulation of glut2 and sglt1 was not blocked by the pretreatment with H89 Fig. The amount of GLUT2 present at the surface of primary goldfish intestinal cells was 1.

The fraction of each glucose transporter at the cell surface was calculated as the ratio of surface to total cellular glucose transporter. This research characterized the cellular distribution of glucose transporters in goldfish intestine, and demonstrated for the first time its regulation by the gut-brain orexigenic hormone ghrelin.

The presence of glucose transporters in the fish intestine has been previously studied using PCR techniques, having been demonstrated that the fish intestinal walls expresses the transporters GLUT2 13 , 47 and SGLT1 Furthermore, some studies using isolated enterocytes 48 and intestinal membrane vesicles preparations 10 have determined the transport rate and so the affinity of these two transporters in fish.

The results of this study showing the presence of these two transporters in the goldfish intestine are in accordance with previous observations, and additionally report the presence of SGLT2 in the intestine. Besides, we offer additional information on their cellular distribution. Specifically, we observed the presence of GLUT2 in the basolateral border and of SGLT1 in the brush border of the mucosal cells, consistent with the putative location previously suggested for these two transporters within the fish enterocyte 48 , and in agreement with the classical model of intestinal glucose absorption in mammals: SGLT1 mediates glucose absorption from the intestinal lumen, whereas GLUT2 provides basolateral exit 3 , According to kinetics studies 10 , 48 , GLUT2 and SGLT1 in fish would function similar to mammals, transporting glucose with low and high affinity, respectively.

However, not only GLUT2 but also SGLT1 and SGLT2 were detected in the basolateral border of the goldfish mucosal cells, suggesting that the three transporters might participate in the transport of glucose from cytosol to the blood in goldfish. Although glucose transporters are mainly present in enterocytes, the presence of some of them, especially SGLT1, has been reported in enteroendocrine cells of both mammals 50 , 51 and fish 14 , It has been suggested that this transporter, together with taste receptors and other G protein-coupled receptor, are present in some enteroendocrine cells as part of the machinery that interacts with chemical food components to trigger the release of gut peptides, such as cholecystokinin, peptide YY, GIP and GLP-1 50 , Results from the present study show that glucose plays an important stimulatory role in the secretion of ghrelin, as well as in the intestinal mRNA expression of preproghrelin, goat and ghs-r1 , in accordance with previous observation in tilapia The fact that the glucose modulation of the ghrelinergic system was observed at all the time points tested indicates a high sensitivity of the ghrelinergic system to glucose and points to a rapid and maintained action of this monosaccharide on the system.

The observed stimulatory effect of glucose on ghrelin might be governed by first an intestinal sensing of the monosaccharide, mechanism by which glucose transporters are known to play a role Using double immunofluorescence, we also observed that a considerable percentage To the best of our knowledge, no studies have previously reported a role for ghrelin in the modulation of glucose transporters in the intestine of any vertebrate.

A role for ghrelin in this function has been shown, however, in other tissues, such as the hypothalamic astrocytes 30 , the white adipocytes 31 , and the cardiomyocytes 32 of mammals, and the hypothalamus and hindbrain of fish Using both in vivo and in vitro approaches, here we demonstrated an important stimulatory role for ghrelin in the gene expression of the three transporters in the intestine of goldfish.

Protein levels of the transporters were also upregulated by ghrelin in vitro. While protein was not quantified in the in vivo study, it is highly likely that the increases in mRNA expression observed in vivo as well as in the rest of the experiments correspond with an increase in protein.

Almost all the changes at the mRNA level observed in vitro extended to proteins. The fact that ghrelin modulates glucose transporters suggests an important role for this hormone on intestinal glucose transport. A hormonal regulation of this process in fish has been suggested previously in a study showing that glucagon, GLP-1, glucocorticoids dexamethasone and catecholamines isoproterenol significantly increase the rate of brush-border glucose transport in the enterocytes of the black bullhead Further studies would be needed to investigate the physiological significance of both anabolic ghrelin and catabolic the others hormones stimulating glucose absorption.

Among the three transporters tested in the present study, SGLT1 seems to be the more sensitive to ghrelin, as its expression was upregulated during all the time points studied. This indicates a chronology in the actions of ghrelin on the different glucose transporters, which might be in accordance with first facilitating the absorption of glucose from the intestinal lumen which is mainly mediated by SGLT1 and then assisting in its transport to the blood.

While ghrelin seems to enhance intestinal glucose absorption, in vivo ghrelin treatment resulted in a decrease in blood glucose levels. This is likely due to similar stimulatory effects of ghrelin on glucose transporters in other locations in order to facilitate glucose absorption into them, so determining an eventual decrease in circulating glucose. One such location seems to be the liver, as supported by the fact that the expression of glut2 and sglt1 are also upregulated by ghrelin in this tissue Supplementary Fig.

The fact that the stimulatory effects of ghrelin on glucose transporters in both the intestine and liver are observed within the same time window suggests that this hormone is simultaneously promoting glucose absorption from the intestinal lumen to the circulation and glucose uptake from the blood to storage locations, thereby preventing a condition of hyperglycemia.

The effects of ghrelin on glycemia seem, however, controversial within the literature, as previous studies have shown that administration of this hormone does not alter circulating glucose levels in rainbow trout 34 while produces a significant increase in tilapia These species-specific discrepancies might be dependent on different dietary habits, although more studies would be needed to elucidate the species- and tissue-specific effects of ghrelin on metabolic partitioning, and glucose production in fishes.

Results presented here demonstrate that all of the observed effects of ghrelin on gene expression are mediated by its receptor GHS-R1a, as all the inductions in expression were abolished by the use of the receptor antagonist [D-Lys3]-GHRP Which intracellular signaling pathway s does this receptor trigger to exert ghrelin actions on glucose transporters? To deepen the knowledge of the mechanisms underlying ghrelin actions on intestinal glucose transporters, our last objective was to determine whether ghrelin modulates transporter translocation into the cell surface.

The translocation of GLUT2 from intracellular vesicles into the plasma membrane has been previously reported in in vivo perfusion studies in rats as a mechanism to allow bulk absorption of glucose by facilitated diffusion after high luminal glucose loads 3 , 5.

This rapid insertion of GLUT2 into the plasma membrane has been shown to be modulated by some hormones, such as glucagon-like peptide 2 GLP-2 , which was reported to promote the translocation of this transporter into the rat jejunal brush-border membrane Findings from the present study represent the first demonstration that ghrelin is able to cause the translocation of GLUT2 in intestinal cells, likely resulting in an improved ability of these cells to take up glucose.

In summary, our data indicate that an important crosstalk between ghrelin and cellular glucose transport occurs in the intestine of goldfish. A proposed model for this crosstalk is summarized in Fig.

First, an increased expression of all components of the ghrelinergic system in the intestine and ghrelin secretion after glucose treatment indicates that this monosaccharide stimulates ghrelin. It is plausible that ghrelin would respond to an increase in glucose by upregulating the expression of its transporters GLUT2, SGLT1 and SGLT2, as well as by promoting the translocation of GLUT2 into the plasma membrane of intestinal cells, all these for facilitating the absorption of glucose.

The involvement of two parameters related to glucosensing in fish GLUT2 and SGLT1; 54 in this sequence of actions could point to a glucosensing response of intestinal cells modulated by ghrelin: intestinal cells would detect changes in glycaemia and respond to them by producing higher levels of ghrelin, which would in turn modulate glucosensing via an action on glucose transporters. Apart from affecting intestinal glucose transport, ghrelin would also facilitate the uptake of glucose from the blood to the hepatic cells, likely helping to avoid a situation of hyperglycemia and to store glucose.

This ghrelinergic regulation of glucose transport would operate during feeding in order to improve nutrient utilization, thus being initiated by the high levels of ghrelin known to be in circulation before a meal Additionally, it has been reported that the ghrelin-induced activation of the glucosensor system in the brain of rainbow trout would eventually lead to an effect on food intake It is thereby possible that this ghrelinergic regulation of intestinal glucose transport relate to the effects of ghrelin on food intake in fish.

On a larger scale, we can also hypothesise that this regulatory mechanism would help fish to cope with the varied food availability situations they have to face in their natural environments.

Overall, these novel results demonstrate that ghrelin plays an important role in glucose transport across the goldfish intestinal walls, thus participating in glucose homeostasis in fish. Further investigations would be needed to test the effects of ghrelin on the transporter activity and to determine whether this peptide is also a modulator of glucose transport in other key organs. This increase in the number of transcripts would also be reflected in the amount of each of the proteins.

Additionally, ghrelin would stimulate the translocation of GLUT2 from intracellular vesicles to the surface of intestinal cells, all of this to facilitate the absorption of glucose. All this ghrelinergic action might be initiated by a glucose-induced upregulation of the intestinal ghrelinergic system.

The protocol for IHC was performed as previously described 61 with slight modifications. In these cases, colocalization was approached by staining consecutive sections with the different antibodies separately. Since heterologous antibodies were used here, it is likely that a certain degree of non-specificity exists in our findings. A separate set of negative control slides were only treated with the secondary antibodies.

All primary and secondary antibodies were diluted in antibody diluent reagent Dako, Mississauga, ON, Canada. These percentages were indicated and shadowed in the corresponding pie-charts. Glucose dose was chosen based on previous studies Injections were carried out at , in h fasted fish, and were performed close to the ventral midline posterior to the pelvic fins.

Injections were performed as described for the previous experiment. Samples of anterior intestine were collected for gene expression analysis see Real-time quantitative PCR section. Tissue culture was performed as previously described for goldfish 64 with slight modifications. Intestine portions from 6 fish were prepared in well multidish plates as described above. Protocol for isolating intestinal cells was adapted from the protocol described by El-Sabry and colleagues 65 in rainbow trout.

The culture medium was changed every day to remove non-adherent cells. Viable intestinal cells were round and characterized by smooth non-folded cell membrane, and they typically achieved confluency on the third day. Briefly, to label the amount of GLUT2, SGLT1 and SGLT2 in the cell surface, cells were blocked, and incubated with primary antibody against each of the glucose transporter dilution; see Immunohistochemistry section for information on antibodies used. Cells were then washed and the fixative was immediately neutralized with glycine.

To label the total cellular amount of each of the glucose transporters, a separate set of intestinal cells were first fixed, quenched in glycine, and then permeabilized. Translocation was quantified as described by Wang and coworkers 67 using standard curves generated with each of the HRP-conjugated secondary antibodies.

The sensitivity of assay was 5. The amount of target peptide was determined by using a cubic regression curve-fit. Primers used for quantifying ghrelin receptor were designed in a region conserved between the ghs-r1a1 and ghs-r1a2 sequences 69 , so PCR products correspond to the sum of all ghs-r1 mRNA isoforms. For Western blot analysis we chose the concentrations and time in which ghrelin exerts the most significant inductions in mRNA expression. Protein extraction and quantification, and Western blot protocol were performed as previously described Blot images were plotted using ImageJ software and band density of vinculin was used to normalize glucose transporters protein density.

Statistical differences between groups were assessed using either t-test for comparisons between two groups or one-way ANOVA followed by Student-Newman-Keuls multiple comparison test for comparisons among multiple groups , after data were checked for normality and homogeneity of variance.

Data that failed one of these requirements were log-transformed and re-checked. All analyses were carried out using SigmaPlot version How to cite this article : Blanco, A. Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Giugliano, D.

Almost all 95 to 98 percent protein is digested and absorbed in the small intestine. The type of carrier that transports an amino acid varies. Most carriers are linked to the active transport of sodium. Short chains of two amino acids dipeptides or three amino acids tripeptides are also transported actively.

However, after they enter the absorptive epithelial cells, they are broken down into their amino acids before leaving the cell and entering the capillary blood via diffusion.

About 95 percent of lipids are absorbed in the small intestine. Bile salts not only speed up lipid digestion, they are also essential to the absorption of the end products of lipid digestion. Short-chain fatty acids are relatively water soluble and can enter the absorptive cells enterocytes directly. The small size of short-chain fatty acids enables them to be absorbed by enterocytes via simple diffusion, and then take the same path as monosaccharides and amino acids into the blood capillary of a villus.

The large and hydrophobic long-chain fatty acids and monoacylglycerides are not so easily suspended in the watery intestinal chyme. However, bile salts and lecithin resolve this issue by enclosing them in a micelle , which is a tiny sphere with polar hydrophilic ends facing the watery environment and hydrophobic tails turned to the interior, creating a receptive environment for the long-chain fatty acids.

The core also includes cholesterol and fat-soluble vitamins. Without micelles, lipids would sit on the surface of chyme and never come in contact with the absorptive surfaces of the epithelial cells. Micelles can easily squeeze between microvilli and get very near the luminal cell surface. At this point, lipid substances exit the micelle and are absorbed via simple diffusion. The free fatty acids and monoacylglycerides that enter the epithelial cells are reincorporated into triglycerides.

The triglycerides are mixed with phospholipids and cholesterol, and surrounded with a protein coat. This new complex, called a chylomicron , is a water-soluble lipoprotein. After being processed by the Golgi apparatus, chylomicrons are released from the cell Figure 6. Too big to pass through the basement membranes of blood capillaries, chylomicrons instead enter the large pores of lacteals.

The lacteals come together to form the lymphatic vessels. The chylomicrons are transported in the lymphatic vessels and empty through the thoracic duct into the subclavian vein of the circulatory system. Once in the bloodstream, the enzyme lipoprotein lipase breaks down the triglycerides of the chylomicrons into free fatty acids and glycerol. These breakdown products then pass through capillary walls to be used for energy by cells or stored in adipose tissue as fat.

Liver cells combine the remaining chylomicron remnants with proteins, forming lipoproteins that transport cholesterol in the blood. Figure 6: Unlike amino acids and simple sugars, lipids are transformed as they are absorbed through epithelial cells. The products of nucleic acid digestion—pentose sugars, nitrogenous bases, and phosphate ions—are transported by carriers across the villus epithelium via active transport.

These products then enter the bloodstream. The electrolytes absorbed by the small intestine are from both GI secretions and ingested foods. Since electrolytes dissociate into ions in water, most are absorbed via active transport throughout the entire small intestine. During absorption, co-transport mechanisms result in the accumulation of sodium ions inside the cells, whereas anti-port mechanisms reduce the potassium ion concentration inside the cells.

To restore the sodium-potassium gradient across the cell membrane, a sodium-potassium pump requiring ATP pumps sodium out and potassium in.

In general, all minerals that enter the intestine are absorbed, whether you need them or not. Iron —The ionic iron needed for the production of hemoglobin is absorbed into mucosal cells via active transport. Once inside mucosal cells, ionic iron binds to the protein ferritin, creating iron-ferritin complexes that store iron until needed. When the body has enough iron, most of the stored iron is lost when worn-out epithelial cells slough off.

When the body needs iron because, for example, it is lost during acute or chronic bleeding, there is increased uptake of iron from the intestine and accelerated release of iron into the bloodstream.

Since women experience significant iron loss during menstruation, they have around four times as many iron transport proteins in their intestinal epithelial cells as do men.

Calcium —Blood levels of ionic calcium determine the absorption of dietary calcium. When blood levels of ionic calcium drop, parathyroid hormone PTH secreted by the parathyroid glands stimulates the release of calcium ions from bone matrices and increases the reabsorption of calcium by the kidneys. PTH also upregulates the activation of vitamin D in the kidney, which then facilitates intestinal calcium ion absorption. The small intestine absorbs the vitamins that occur naturally in food and supplements.

Fat-soluble vitamins A, D, E, and K are absorbed along with dietary lipids in micelles via simple diffusion. This is why you are advised to eat some fatty foods when you take fat-soluble vitamin supplements. Most water-soluble vitamins including most B vitamins and vitamin C also are absorbed by simple diffusion. An exception is vitamin B 12 , which is a very large molecule. Intrinsic factor secreted in the stomach binds to vitamin B 12 , preventing its digestion and creating a complex that binds to mucosal receptors in the terminal ileum, where it is taken up by endocytosis.

Each day, about nine liters of fluid enter the small intestine. About 2. About 90 percent of this water is absorbed in the small intestine. Water absorption is driven by the concentration gradient of the water: The concentration of water is higher in chyme than it is in epithelial cells. Thus, water moves down its concentration gradient from the chyme into cells. As noted earlier, much of the remaining water is then absorbed in the colon. All substances that move through the membrane do so by one of two general methods, which are categorized based on whether or not energy is required.

Passive transport is the movement of substances across the membrane without the expenditure of cellular energy. In contrast, active transport is the movement of substances across the membrane using energy from adenosine triphosphate ATP. In order to understand how substances move passively across a cell membrane, it is necessary to understand concentration gradients and diffusion. A concentration gradient is the difference in concentration of a substance across a space.

When molecules move in this way, they are said to move down their concentration gradient. Diffusion is the movement of particles from an area of higher concentration to an area of lower concentration. A couple of common examples will help to illustrate this concept. Imagine being inside a closed bathroom. If a bottle of perfume were sprayed, the scent molecules would naturally diffuse from the spot where they left the bottle to all corners of the bathroom, and this diffusion would go on until no more concentration gradient remains.

Another example is a spoonful of sugar placed in a cup of tea. Eventually the sugar will diffuse throughout the tea until no concentration gradient remains. In both cases, if the room is warmer or the tea hotter, diffusion occurs even faster as the molecules are bumping into each other and spreading out faster than at cooler temperatures. Having an internal body temperature around Visit this link to see diffusion and how it is propelled by the kinetic energy of molecules in solution.

How does temperature affect diffusion rate, and why? Whenever a substance exists in greater concentration on one side of a semipermeable membrane, such as the cell membranes, any substance that can move down its concentration gradient across the membrane will do so.

Consider substances that can easily diffuse through the lipid bilayer of the cell membrane, such as the gases oxygen O 2 and CO 2. O 2 generally diffuses into cells because it is more concentrated outside of them, and CO 2 typically diffuses out of cells because it is more concentrated inside of them. Neither of these examples requires any energy on the part of the cell, and therefore they use passive transport to move across the membrane. Before moving on, you need to review the gases that can diffuse across a cell membrane.

Because cells rapidly use up oxygen during metabolism, there is typically a lower concentration of O 2 inside the cell than outside. As a result, oxygen will diffuse from the interstitial fluid directly through the lipid bilayer of the membrane and into the cytoplasm within the cell.

On the other hand, because cells produce CO 2 as a byproduct of metabolism, CO 2 concentrations rise within the cytoplasm; therefore, CO 2 will move from the cell through the lipid bilayer and into the interstitial fluid, where its concentration is lower. This mechanism of molecules moving across a cell membrane from the side where they are more concentrated to the side where they are less concentrated is a form of passive transport called simple diffusion Figure 3.

Large polar or ionic molecules, which are hydrophilic, cannot easily cross the phospholipid bilayer. Very small polar molecules, such as water, can cross via simple diffusion due to their small size.

Charged atoms or molecules of any size cannot cross the cell membrane via simple diffusion as the charges are repelled by the hydrophobic tails in the interior of the phospholipid bilayer. Solutes dissolved in water on either side of the cell membrane will tend to diffuse down their concentration gradients, but because most substances cannot pass freely through the lipid bilayer of the cell membrane, their movement is restricted to protein channels and specialized transport mechanisms in the membrane.

A common example of facilitated diffusion is the movement of glucose into the cell, where it is used to make ATP.

Although glucose can be more concentrated outside of a cell, it cannot cross the lipid bilayer via simple diffusion because it is both large and polar. To resolve this, a specialized carrier protein called the glucose transporter will transfer glucose molecules into the cell to facilitate its inward diffusion.

There are many other solutes that must undergo facilitated diffusion to move into a cell, such as amino acids, or to move out of a cell, such as wastes. Because facilitated diffusion is a passive process, it does not require energy expenditure by the cell. Water also can move freely across the cell membrane of all cells, either through protein channels or by slipping between the lipid tails of the membrane itself.

Osmosis is the diffusion of water through a semipermeable membrane Figure 3. The movement of water molecules is not itself regulated by some cells, so it is important that these cells are exposed to an environment in which the concentration of solutes outside of the cells in the extracellular fluid is equal to the concentration of solutes inside the cells in the cytoplasm.

Two solutions that have the same concentration of solutes are said to be isotonic equal tension. When cells and their extracellular environments are isotonic, the concentration of water molecules is the same outside and inside the cells, and the cells maintain their normal shape and function.

Osmosis occurs when there is an imbalance of solutes outside of a cell versus inside the cell. A solution that has a higher concentration of solutes than another solution is said to be hypertonic , and water molecules tend to diffuse into a hypertonic solution Figure 3. Cells in a hypertonic solution will shrivel as water leaves the cell via osmosis.

In contrast, a solution that has a lower concentration of solutes than another solution is said to be hypotonic , and water molecules tend to diffuse out of a hypotonic solution.

Cells in a hypotonic solution will take on too much water and swell, with the risk of eventually bursting. Various organ systems, particularly the kidneys, work to maintain this homeostasis. Another mechanism besides diffusion to passively transport materials between compartments is filtration. Unlike diffusion of a substance from where it is more concentrated to less concentrated, filtration uses a hydrostatic pressure gradient that pushes the fluid—and the solutes within it—from a higher pressure area to a lower pressure area.

Filtration is an extremely important process in the body.