The lacteal is surrounded by the capillaries. Digested nutrients pass into the blood vessels in the wall of the intestine through a process of diffusion. The inner wall, or mucosa, of the small intestine is lined with simple columnar epithelial tissue.

Structurally, the mucosa is covered in wrinkles or folds called plicae circulares—these are permanent features in the wall of the organ. They are distinct from the rugae, which are non-permanent features that allow for distention and contraction.

From the plicae circulares project microscopic finger-like pieces of tissue called villi Latin for shaggy hair. The individual epithelial cells also have finger-like projections known as microvilli. The function of the plicae circulares, the villi, and the microvilli is to increase the amount of surface area available for the absorption of nutrients.

Each villus has a network of capillaries and fine lymphatic vessels called lacteals close to its surface. The epithelial cells of the villi transport nutrients from the lumen of the intestine into these capillaries amino acids and carbohydrates and lacteals lipids.

The absorbed substances are transported via the blood vessels to different organs of the body where they are used to build complex substances, such as the proteins required by our body.

The food that remains undigested and unabsorbed passes into the large intestine. Absorption of the majority of nutrients takes place in the jejunum, with the following notable exceptions:. Section of duodenum : Section of duodenum with villi at the top layer. Search site Search Search.

Go back to previous article. Sign in. Learning Objectives Describe the role played by the small intestine in the absorption of nutrients. As a result, meals with adequate fiber depress the rate at which carbohydrates elevate blood glucose levels as well as prolong the sense of satisfaction or satiety generated by a full stomach.

By moderating the rate at which chyme passes into the small intestine, where carbohydrates are digested and absorbed. Overall, an additional three to ten hours is needed for your meal to traverse the large intestine and complete its journey.

An additional one to two days may pass before residues that are mostly fiber leave your body. Chewed food is swallowed as a lump, or bolus, which the muscles of the gastrointestinal tract push in a wavelike motion past the epiglottis, through the esophagus, and into the stomach.

Swallowing causes a temporary relaxation of the LES, which returns to a contracted state after the bolus passes into the stomach.

Gastroesophageal reflux disease GERD happens when stomach contents pass back through the LES into the esophagus, causing heartburn and regurgitation. GERD treatment includes behavioral modification and medications that reduce stomach acid content.

The stomach continues the breakdown of foods that started with chewing. Hydrochloric acid in the stomach denatures food proteins, making them more digestible, and inhibits bacterial growth, which reduces the risk of foodborne illness.

Gastrin, somatostatin, and ghrelin manage stomach function, while pepsinogen is activated to make pepsin, which begins the enzymatic breakdown of protein. Stomach contractions move the mixture of food and gastric juices into the small intestine, where further digestion takes place.

The vast majority of the nutrients that we get from our food and drink are absorbed in the small intestine. An amazing list of hormones, enzymes, emulsifiers, and carrier molecules makes this possible. Even though fat, carbohydrates, and protein are absorbed in the small intestine, much work remains for the large intestine, where fiber supports beneficial bacteria, water is conserved through absorption, and digestive residues are prepared for excretion.

The small intestine is the primary site for the digestion and eventual absorption of nutrients. In fact, over 95 percent of the nutrients gained from a meal, including protein, fat, and carbohydrate, are absorbed in the small intestine.

Alcohol, an additional source of energy, is largely absorbed in the small intestine, although some absorption takes place in the mouth and stomach as well.

Three organs of the body assist in digestion: the liver, the gall bladder, and the pancreas. The liver produces bile, a substance that is crucial to the digestion and absorption of fat, and the gall bladder stores it. The pancreas provides bicarbonate and enzymes that help digest carbohydrates and fat.

The liver, gall bladder, and pancreas share a common duct into the small intestine, and their secretions are blended. If the common duct becomes blocked, as with a gall stone, adequate bile is not available, and the digestion of fat is seriously reduced, leading to cramping and diarrhea.

Bicarbonate secreted by the pancreas neutralizes chyme makes it less acidic and helps create an environment favorable to enzymatic activity. The pancreas provides lipase, an enzyme for digesting fat, and amylase for digesting polysaccharides carbohydrate. The small intestine produces intermediate enzymes, such as maltase, that digest maltose and peptidase to break down proteins further into amino acids.

The villi are fingerlike projections from the walls of the small intestine. They are a key part of the inner surface and significantly increase the absorptive area. A large surface area is important to the speed and effectiveness of digestion. Some medical treatments, such as radiation therapy, can damage villi and impair the function of the small intestine.

Diseases also affect villi health. One sign of chronic alcoholism is blunted villi that lack adequate surface area, resulting in poor absorption of nutrients. Someone in the advanced stages of alcoholism often experiences diarrhea due to reduced water and sodium absorption, poor eating habits that limit vitamin C intake coupled with an increased loss in urine, and zinc deficiency due to poor absorption.

Cells in the villi are continuously exposed to a harsh environment and, as a result, have a short life-span of about three days. Adequate nutrition is required for optimal health and to ensure that new cells are ready to replace aging ones. Insufficient protein in the diet depresses cell replacement and reduces the efficiency of absorption, thereby further compromising overall health.

This is a significant issue for people who have experienced starvation. A quick introduction of large amounts of food can result in cramping and diarrhea, further threatening survival. Enzymes are biological catalysts that speed up reactions without being changed themselves. Enzymes produced by the stomach, pancreas, and small intestine are critical to digestion.

For example, carbohydrates are large molecules that must be broken into smaller units before absorption can take place.

Enzymes such as amylase, lactase, and maltase catalyze the breakdown of starches polysaccharides and sugars disaccharides into the monosaccharides, glucose, galactose, and fructose.

Proteases such as pepsin and trypsin digest protein into peptides and subsequently into amino acids, and lipase digests a triglyceride into a monoglyceride and two fatty acids. The digestion of fat poses a special problem because fat will not disperse, or go into solution, in water.

The lumen of the small intestine is a liquid or watery environment. This problem is solved by churning, the action of enzymes, and bile salts secreted by the liver and gall bladder. Bile acts as an emulsifier, or a substance that allows fat to remain in suspension in a watery medium. The resulting micelle, or a droplet with fat at the center and hydrophilic or water-loving phospholipid on the exterior, expedites digestion of fats and transportation to the intestinal epithelial cell for absorption.

Nutrients truly enter the body through the absorptive cells of the small intestine. Absorption of nutrients takes place throughout the small intestine, leaving only water, some minerals, and indigestible fiber for transit into the large intestine.

There are three mechanisms that move nutrients from the lumen, or interior of the intestine, across the cell membrane and into the absorptive cell itself. They are passive, facilitated, and active absorption. In passive absorption, a nutrient moves down a gradient from an area of higher concentration to one of lower concentration.

For this downhill flow, no energy is required. Fat is an example of a nutrient that is passively absorbed. In facilitated absorption, a carrier protein is needed to transport a nutrient across the membrane of the absorptive cell.

For this type of absorption, no energy is required. Fructose is an example of a nutrient that undergoes facilitated absorption. In active absorption, both a carrier protein and energy are needed. Active absorption rapidly moves a nutrient from an area of low concentration in the lumen to an area of high concentration in the cell and eventually into the blood.

Glucose and galactose are examples of nutrients that require active absorption. The large intestine completes the process of absorption. In the upper large intestine, most of the remaining water and minerals are absorbed.

Fiber becomes a food source for resident bacteria that generate gas and acids as by-products as well as some vitamins. Over four hundred different bacteria colonize the colon, or large intestine, and provide the body with vitamin K and vitamin B12 as by-products of their life processes.

The normal flora, or bacteria, that reside in the intestine also resist colonization efforts of other, unfamiliar bacteria. Finally, the residues of a meal move into the rectum and are further concentrated and prepared for expulsion from the body as feces.

Did you know that the gastrointestinal tract of a newborn baby is sterile? Exposure to the world and the first swallow of milk changes everything by introducing bacteria. A breastfed baby tends to have a more stable and uniform microbiota than a formula-fed infant, and this is advantageous.

The protective influence of breastfeeding reduces the incidence of diarrhea and modifies the risk of allergic diseases during childhood. Exclusive breastfeeding during the first six months of life is recommended by the World Health Organization followed by supplemental breastfeeding throughout the first two years of life.

Getting the energy and nutrients that we need from our food and drink is a complex process that involves multiple organs and an array of substances. The small intestine is a muscular tube with villi projecting into the lumen that vastly increase its absorptive surface area.

The liver produces bile, which the gall bladder stores and secretes into to small intestine via a common duct. Bile is an emulsifier that suspends fats in the watery chyme, making enzymatic breakdown possible.

The pancreas produces lipase and secretes it into a common duct, where it is delivered to the small intestine. Lipase breaks down large fat molecules into manageable parts. The large intestine plays an important part in concentrating the residues of digestion and conserving water through absorption.

It also is a home for beneficial bacteria that are nourished by fiber that is indigestible for humans. Nutrition for Consumers by University of North Texas is licensed under a Creative Commons Attribution-NonCommercial 4.

Skip to content Increase Font Size. Objectives Describe the role of the mouth, teeth, tongue, epiglottis, and esophagus in chewing, lubricating, and delivering food and drink to the stomach and beyond Explain the cause of heartburn or gastroesophageal reflux disease Associate the small intestine and villi with their digestive role Connect the large intestine to its function 3.

Nutrients as Raw Materials Nutrients are provided by the foods that you eat. Digestion Begins Digestion begins in your mouth as you chew or masticate food and mix it with saliva. Mobility Working together, cheek muscles and the tongue position a lump of food for swallowing.

Tongue and Taste The tongue is instrumental in the perception of taste. Summary Digestion is a process that transforms the foods that we eat into the nutrients that we need.

Key Concepts The muscular tube called the epiglottis The esophagus and lower esophageal pressure Introduction to the stomach The Epiglottis The esophagus is a muscular tube that connects the mouth to the stomach.

The Esophagus Passage of a bolus or lump of food through the esophagus is aided by 1 muscular contractions, 2 the mucus lining of the esophagus, and 3 gravity. Foods and Regurgitation A reduced LES pressure, or tone, reduces its ability to tightly constrict and increases the likelihood that you will regurgitate or burp.

Mucus and Stomach Health The mucus layer lining the esophagus serves to lubricate a passing bolus of food, but the thicker mucus layer that lines the stomach has a different task. The Amazing Stomach The stomach is a J-shaped pouch positioned between the esophagus and the small intestine.

Workings of the Stomach After mixing is complete, the stomach moves food and gastric secretions to the small intestine in a watery solution called chyme. Summary Chewed food is swallowed as a lump, or bolus, which the muscles of the gastrointestinal tract push in a wavelike motion past the epiglottis, through the esophagus, and into the stomach.

Key Concepts Functions of the small intestine Role of liver, gall bladder, and pancreas in digestion Actions of enzymes, hormones, and emulsifiers Functions of the large intestine Gut microflora and breastfeeding The Small Intestine The small intestine is the primary site for the digestion and eventual absorption of nutrients.

Liver, Gall Bladder, Pancreas Three organs of the body assist in digestion: the liver, the gall bladder, and the pancreas. Neutralizing Chyme Bicarbonate secreted by the pancreas neutralizes chyme makes it less acidic and helps create an environment favorable to enzymatic activity.

Wonders of the Villi The villi are fingerlike projections from the walls of the small intestine. The Enzymes of Digestion Enzymes are biological catalysts that speed up reactions without being changed themselves. Digestion of Fat The digestion of fat poses a special problem because fat will not disperse, or go into solution, in water.

Rate of Absorption Nutrients truly enter the body through the absorptive cells of the small intestine. The Large Intestine The large intestine completes the process of absorption. GIT and Breastfeeding Did you know that the gastrointestinal tract of a newborn baby is sterile?

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The small intestine is highly efficient at this, absorbing monosaccharides at an estimated rate of grams per hour. All normally digested dietary carbohydrates are absorbed; indigestible fibers are eliminated in the feces. The monosaccharides glucose and galactose are transported into the epithelial cells by common protein carriers via secondary active transport that is, co-transport with sodium ions.

The monosaccharides leave these cells via facilitated diffusion and enter the capillaries through intercellular clefts.

The monosaccharide fructose which is in fruit is absorbed and transported by facilitated diffusion alone. The monosaccharides combine with the transport proteins immediately after the disaccharides are broken down. Active transport mechanisms, primarily in the duodenum and jejunum, absorb most proteins as their breakdown products, amino acids.

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.

The small intestine is the site of most chemical digestion and almost all absorption. Chemical digestion breaks large food molecules down into their chemical building blocks, which can then be absorbed through the intestinal wall and into the general circulation.

Intestinal brush border enzymes and pancreatic enzymes are responsible for the majority of chemical digestion. The breakdown of fat also requires bile. Most nutrients are absorbed by transport mechanisms at the apical surface of enterocytes. Exceptions include lipids, fat-soluble vitamins, and most water-soluble vitamins.

With the help of bile salts and lecithin, the dietary fats are emulsified to form micelles, which can carry the fat particles to the surface of the enterocytes. There, the micelles release their fats to diffuse across the cell membrane. The fats are then reassembled into triglycerides and mixed with other lipids and proteins into chylomicrons that can pass into lacteals.

Other absorbed monomers travel from blood capillaries in the villus to the hepatic portal vein and then to the liver. Review Questions. Where does the chemical digestion of starch begin?

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Copyright © , StatPearls Publishing LLC. Bookshelf ID: NBK PMID: PubReader Print View Cite this Page Basile EJ, Launico MV, Sheer AJ. In response to high-fat feeding or obesity, small intestinal SGLT1 expression is reduced, leading to an impairment of glucose sensing, GLP-1 secretion, and glucose control.

c Mechanisms of small intestinal protein sensing. Luminal small oligopeptides and amino acids are taken up by PepT1 and amino acid transporters, respectively, into the enterocyte and enteroendocrine cells. Small intestinal protein sensing stimulates the release of CCK and GLP-1 and regulates feeding and glucose homeostasis potentially via PepT1 dependent mechanisms.

In addition, amino acids stimulate peptide release via the membrane-bound calcium-sensing receptor, the umami taste receptor, and G-protein-coupled receptor 6A. However, the downstream mechanism mediating the peptide release remains elusive. In parallel, amino acids are also transported to the basolateral side, and studies implicated that they may activate the calcium-sensing receptor to stimulate GLP-1 secretion.

Vagal afferent fibers mediate the anorectic effects of intestinal lipid-sensing and are activated by several gut peptides Vagal afferents contain CCK-1 receptor CCK-1R and selective knockdown of CCK-1R in vagal afferents abolishes the ability of CCK to lower food intake However, the impact of vagal CCK-1R on small intestinal lipid-induced CCK signaling has not been established Vagal afferents also express GLP-1R 42 , and at least one study reports that GLP-1 signaling mediates the suppressive effects of jejunal linoleic acid infusion However, GLP-1R-expressing vagal afferent neurons were also reported to detect stomach and intestinal stretch but have no impact on nutrient-sensing Thus, the effect of GLP-1R on intestinal lipid sensing remains unclear.

It is possible that the enteric nervous system, which contains GLP-1R, may mediate the gut—brain effect instead 18 , Utilizing pancreatic—euglycemic clamps with plasma insulin levels maintained at a basal non-stimulated condition, upper small intestinal lipid infusion lowers hepatic glucose production In contrast, a study with human participants reports that during the pancreatic—euglycemic clamps, no difference in glucose production is detected in response to intraduodenal infusion of lipid vs control group However, this observation is made in the presence of a progressive rise in plasma insulin and glucose levels prior to the start of the lipid or control infusion, and a parallel progressive drop in both plasma free fatty acids and glucose production in both groups Thus, it is not surprising that glucose production is not further lowered by intraduodenal lipid vs.

saline infusion in a state that mimics the postprandial state, in which hepatic glucose production is already inhibited. Similar to lipid-induced reductions in food intake, the ability of small intestinal lipid infusion to lower hepatic glucose production is dependent on CCK and GLP-1 signaling during the pancreatic basal insulin -euglycemic clamps 45 , Further, inhibiting CCK-1R signaling during refeeding, which activates nutrient-sensing pathways, results in postprandial hyperglycemia The specific mechanisms leading to the release of CCK and subsequent effects on glucose homeostasis are not fully understood, although the esterification of fatty acids to fatty acyl-CoA via acyl-CoA synthetase and the subsequent activation of mucosal protein kinase C PKC -δ are necessary for rats 46 , This is consistent with the fact that LCFA induces CCK release in intestinal secretin tumor cells via PKC-δ activation In parallel, the formation of chylomicron is also implicated in CCK release 50 , but the underlying mechanisms of how lipids stimulate CCK to release overall remain elusive Fig.

Further, the specific role of vagal GLP-1R signaling in mediating the glucoregulatory effect of lipids remains to be clarified. In addition to lowering hepatic glucose production via a gut—brain axis 45 , 46 , small intestinal lipid-sensing could regulate glucose homeostasis via GLPinduced increase in insulin or suppression of glucagon secretion, as lipid-sensing increases GLP-1 release 45 ,.

However, GLP-1 induced increase in insulin secretion requires the presence of elevated circulating glucose levels Thus, it is possible that while an infusion of lipid alone increases GLP-1, this would not substantially elevate plasma insulin levels in the absence of a concomitant rise in blood glucose levels, as reported in human studies 52 , Despite this, increasing circulating active GLP-1 levels during an Intralipid intestinal infusion via DPP-IV inhibition inhibits degradation of GLP-1 decreases glucose and increases insulin levels In addition, while GLP-1 is known to suppress glucagon secretion, glucagon is consistently increased with Intralipid infusion 52 , Although it has not been evaluated, this unexpected effect of Intralipid on glucagon could be due to the concurrent CCK release, as CCK lowers the inhibitory effect of glucose on glucagon secretion A high-fat diet HFD impairs lipid-induced gut—brain feedback regulating both energy and glucose homeostasis.

Intestinal sensing of lipids is impaired during HFD in both rodents and humans 55 , however, it is still contentious as to whether this is due to chronic exposure to HFD or induction of obesity. For example, studies in rats have shown that the combination of an HFD with a genetic background that is predisposed to obesity, is associated with reduced intestinal-lipid sensing 56 , Furthermore, HFD decreases postprandial active GLP-1 and CCK levels in obese-prone rats compared to obese-resistant rats, potentially due to decreased intestinal expression of GPR40 and GPR, receptors that are implicated in lipid-sensing induced secretion of gut peptides 56 , 57 , 58 Fig.

The importance of interaction between diet and obesity for nutrient-sensing is also supported by human data. A 2-week high-fat dietary regimen in humans does not impair the suppressive effects on appetite or the CCK and GLP-1 response to an intralipid duodenal infusion However, individuals with obesity are less responsive to the satiating effects of dietary fat 60 , Obesity is also associated with reduced postprandial gut peptide levels 62 , and specifically for lipid-sensing, CCK release is blunted in individuals affected by obesity following intraduodenal oleic acid Therefore, future studies need to delineate the effect of diet vs.

phenotype, which may be due to the ability of the gut microbiota to mediate this interaction between the diet and host physiology discussed in more detail below. Besides reductions in lipid-induced gut peptide release, it is possible that diminished sensitivity to gut peptides contributes to the reduced responsiveness to intestinal fat sensing in feeding control.

The anorectic effect of CCK is impaired in HFD-fed mice and rats 55 , as is vagal afferent activation 55 , although this has not been fully examined in humans. Further, CCK-1R expression in vagal nerves is decreased in HFD induced obese rats 56 , ultimately contributing to reduced nodose ganglia cocaine and amphetamine-regulated transcript CART expression, a neuropeptide regulating energy homeostasis, in association with increased food intake and body weight However, vagal CCK resistance during obesity could also be due to obesity-associated leptin resistance, as the leptin receptor is co-expressed with CCK-1R in the vagal afferent neurons 65 and leptin potentiates the suppressive effect of CCK on appetite and increases vagal afferent activation following CCK administration 66 , Using both genetic and viral approaches, the knockdown of leptin receptors in vagal afferent neurons impairs CCK responsiveness and induces hyperphagia Taken together, it is possible that impairments in CCK signaling both at the level of secretion and vagal activation could drive reduced lipid-induced satiation, although much of this remains to be tested in humans.

HFD also impairs the ability of upper small intestinal lipid sensing to improve glucose tolerance and lower hepatic glucose production 45 , The loss of effect of lipid-sensing following short-term 3-day HF feeding is partly due to impaired vagal CCK-1R signaling as both Intralipid and CCK but not upstream activation of vagal protein kinase A fail to lower glucose production in HF rats 25 , 46 , In parallel, HFD lowers upper small intestinal long-chain acyl-CoA synthetase-3 expression and disrupts long-chain acyl-CoA synthetase-3 dependent small intestinal fatty acid metabolism to regulate glucose homeostasis.

However, transplantation of healthy microbiome to HF rats rescues the glucoregulatory effect of lipid-sensing via upregulation of long-chain acyl-CoA synthetase-3 expression in a small intestinal farnesoid x receptor FXR dependent fashion The underlying mechanism of how HF-induced changes in small intestinal microbiome alter bile acid pool, FXR, acyl-CoA synthetase-3, and lipid sensing remains elusive.

Nonetheless, we hypothesize that enhancing long-chain acyl-CoA synthetasedependent upper small intestinal fatty acid metabolism could increase GLP1 action to regulate glucose homeostasis in spite of CCK-1R vagal resistance Fig.

Intraduodenal infusion of glucose dose-dependently suppresses food intake in rodents 72 , and reduces food intake 73 , 74 or favorably influences subjective appetite ratings 73 in humans. Intravenous infusion of glucose to match the levels observed in blood following intestinal infusion of glucose does not inhibit food intake in rodents and humans 72 , 75 , highlighting the role of preabsorptive intestinal glucose-sensing.

GLP-1R antagonist Exendin-9 abolishes the anorectic effect of both intragastric and voluntary sucrose loads in rats 76 , indicating that GLP-1 action mediates the effect of carbohydrate-sensing on food intake. Glucose-induced GLP-1 secretion from small intestinal EECs is dependent on sodium-glucose luminal transporter-1 SGLT-1 As non-metabolizable sugars transported via SGLT-1 also induce GLP-1 release 79 , glucose-sensing appears to be dependent on the transport of glucose via SGLT-1 but independent of subsequent cellular glucose metabolism.

This finding has been confirmed in the human small intestine However, recent studies report that non-caloric sweeteners do not induce GLP-1 release in primary L-cells and rodents 79 , 83 , and in humans, noncaloric sweeteners fail to induce gut peptide release and have no effect on appetite It is possible that the suppressive effect of glucose on food intake depends on the specific site of the small intestine where glucose is sensed.

For instance, a greater reduction of energy intake associates with higher CCK levels in humans receiving duodenal versus jejunal infusion of glucose However, in another study 86 , glucose infusion into the ileum, but not duodenum, suppresses food intake, and a rodent study similarly found that ileal glucose infusion suppresses food intake to a greater degree than duodenal glucose infusion These studies support the notion that ileal nutrient-sensing regulates gut motility 88 but later proposed by many to also regulate food intake In contrast to the upper small intestine, this may be due to SGLT-1 independent glucose-mediated GLP-1 release 90 Fig.

Small intestine infusion of glucose impacts glucose homeostasis and the effects are not only due to glucose absorption into circulation. First, it is well established that the GI tract contributes to insulin secretion via the incretin effects of GLP-1 and GIP, which stimulate insulin secretion from the pancreas.

Direct infusion of glucose into the duodenum in humans also increases circulating insulin levels, as does jejunal infusions, while glucagon levels either decrease or remain unchanged This discrepancy in glucagon is likely due to the differing actions of GIP and GLP-1, as GIP paradoxically increases while GLP-1 inhibits glucagon secretion While both GLP-1R and GIPR knockout mice exhibit reduced insulin release in response to intestinal glucose, each model only exhibits mild glucose intolerance.

However, dual GLP-1R and GIPR knockout mice exhibit substantially impaired glycemic control and oral glucose-stimulated insulin release as compared to single incretin receptor knockout mice Further, GIP was found to be a more powerful incretin hormone than GLP-1, but its overall effect on glucose homeostasis is likely masked by the concomitant rise in glucagon As such, the common hepatic branch of the vagus, as well as celiac and gastric branches, are all implicated in contributing to the glucoregulatory effects of GLP-1 action 94 , For example, selective knockdown of GLP-1R in the nodose ganglia impairs glucose response to a mixed meal but interestingly does not impair oral glucose tolerance This implies that the impaired response to a mixed meal challenge is not dependent on altered intestinal glucose-sensing.

Further, the impact of genetic knockout of GLP-1R in vagal neurons on oral glucose tolerance is contentious 22 , However, selective restoration of the islet and pancreatic duct GLP-1R in global GLP-1R knockout mice was sufficient to improve impaired oral glucose tolerance, although the reason for this is unknown as there was no change in glucose-stimulated insulin release among the groups Thus, the mechanism of glucose-induced GLP-1 regulation on insulin secretion remains elusive.

Direct infusion of glucose into the upper small intestine or jejunum given at a dose that does not increase portal glucose levels activates small intestinal SGLT-1 and lowers hepatic glucose production in parallel to an increase in portal GLP-1 levels 97 , 98 Fig.

Similar to the mechanism of glucose-sensing in the regulation of food intake, infusion of non-metabolizable sugar 3-OMG that is transported via SGLT-1 into the upper small intestine recapitulates the glucoregulatory effect of glucose-sensing 97 , suggesting that upper small intestinal glucose-sensing in inducing GLP-1 release is dependent on the electrogenic capacity of SGLT-1 but independent of cellular glucose metabolism.

Further, the effect of small intestinal glucose sensing on hepatic glucose production regulation is abolished when glucose is co-infused with GLP-1R antagonist exendin-9 97 , strengthening the role of GLP-1 as the mediator of intestinal glucose-sensing on hepatic glucose production Despite the prevalence of carbohydrates in the diet, few studies have investigated the effect of obesity or HFD on intestinal glucose sensing.

In rodents, both diet-induced and genetic models of obesity exhibit reduced satiation in response to intraduodenal carbohydrate infusion, although the effect is less pronounced than what is observed with intestinal lipids and is observed in some but not all studies 57 , Moreover, there are no differences in the response to duodenal infusion of glucose between participants with and without obesity In contrast, obesity is associated with reduced postprandial GLP-1 levels and sensitivity to GLP-1 in rodents , , although gut peptides other than GLP-1 may mediate the anorectic effect of intestinal carbohydrates Despite these unknowns, research with human participants suggests that the incretin effect is impaired in diabetes, which is likely due to reduced GLP-1 secretion and impaired potency of GLP-1 to induce insulin secretion Similarly, HFD in rodents impairs the ability of upper small intestinal glucose infusion to lower glucose production, likely due to reduced GLP-1 secretion This reduction in GLP-1 secretion during HFD is associated with decreased upper small intestinal SGLT-1 levels In line with this, HFD reduces SGLT1 expression in small intestinal L-cells, resulting in impaired GLP-1 response to glucose in primary cultures Fig.

High protein diets in both humans and rodents reduce body weight and adiposity in association with intestinal protein sensing-related increases in gut peptide levels. In humans, duodenal infusion of whey protein hydrolysate decreases food intake without a change in subjective appetite ratings , but in parallel to increased GLP-1 and CCK levels , In addition, casein infusion into the ileum of humans also decreases food intake, whereas infusion into the duodenum or jejunum has minimal effect.

This is possibly explained by the fact that ileal casein infusion resulted in the greatest rise in GLP-1 levels compared to duodenal or jejunal infusion In rodents, various protein solutions potentially reduce food intake more potently than isocaloric and isovolumetric carbohydrate infusions , and the underlying mechanisms may involve CCK release and subsequent activation of CCK-1R on vagal afferent neurons , , , although GLP-1R signaling was not investigated.

Thus, future studies are needed to more definitively identify the specific effects of different types of protein and the intestinal site of protein sensing on the regulation of food intake and gut peptide release. High protein diets improve glucose homeostasis in both rodents and humans , , even in the absence of weight loss in patients with diabetes or during pair-feeding in rodents , In humans, duodenal whey protein hydrolysate impacts circulating glucose, insulin, and glucagon , , while duodenal, jejunal, or ileal casein infusion leads to a substantial increase in insulin levels with no change in glucose Moreover, infusion of leucine alone into the duodenum dose-dependently increases insulin, with slight decreases in glucose, but no change in glucagon These effects are mediated by peptide transporter-1 PepT1 , a di- and tri-peptide proton-coupled transporter located in the brush border membrane of the intestinal epithelium Fig.

Recent evidence using isolated intestinal perfusion technique indicates that dietary protein induces gut peptide secretion via transport of oligopeptides into cells via PepT1. Cellular oligopeptides are broken down into individual amino acids that are released to the basolateral side of the intestine to activate amino acid receptors Taken together, these data indicate that both apical PepT1 and basolateral CaSR could be critical for peptone-mediated GLP-1 release Fig.

Nonetheless, more work is needed to determine the exact mechanism linking intestinal protein sensing to gut peptide release, and which specific amino acids and sensors are required. In contrast to lipids and carbohydrates, sensitivity to intestinal protein-sensing appears to be maintained during obesity, highlighting the potential of protein-sensing as a therapeutic target for weight loss.

There are no differences in energy intake or CCK and GLP-1 responses between individuals with and without obesity following intraduodenal whey protein infusion In line with this data, rats fed an HFD for either 3 or 28 days, with the latter resulting in increased adiposity, still responded to small intestinal casein infusion by lowering hepatic glucose production In addition, high protein intake improves metabolic outcomes, like body weight, adiposity, insulin sensitivity, and food intake, in both rodents and humans , , , and improves glucose tolerance and lowers blood glucose levels in patients with diabetes This may be explained by the fact that intestinal proteins more potently stimulate gut peptide secretion as compared to isocaloric lipids or carbohydrates Future research is warranted to uncover the mechanisms of how intestinal protein sensing, but not lipid or carbohydrate sensing, is maintained during metabolic dysregulation.

Changes in the gut microbiota affect obesity and related metabolic disorders, and the mechanisms linking the gut microbiota to energy and glucose homeostasis have been extensively reviewed , However, the majority of the studies have focused on the role of the microbiota in the large intestine, and few studies have examined the metabolic impact of the small intestinal microbiota.

While there are several orders of magnitude greater abundance of bacteria in the large intestine than in the small intestine, nutrient-sensing, and gut—brain feedback mechanisms are localized to the small intestine, as nutrient absorption limits ingested macronutrients from reaching the large intestine.

Further, the protective barrier of a mucus layer in the small intestine is much less established , allowing for an increased potential for intimate interactions between the host epithelial cells and the gut bacteria. For example, restoring the gut microbiome in germ-free mice results in an acute, transient phase, followed by a homeostatic phase that impacts jejunal transcriptomics and metabolomics involved in lipid and glucose metabolism and uptake However, the initial acute response is not observed in the ileum or colon, highlighting the sensitivity of the upper small intestine to the microbiome.

Evidence suggests that the microbiota could also greatly impact nutrient-sensing mechanisms. First, microbial metabolites, especially short-chain fatty acids SCFAs , are known to induce gut peptide secretion from EECs , Most bacterially derived metabolites like SCFAs are produced predominantly in the distal intestine but are also present in small amounts in the ileum and can reduce glucose production via a gut—brain axis , Other metabolites, like indole, are highly abundant in the small intestine and also regulate GLP-1 release from EECs Secondly, the gut microbiota impacts EEC physiology.

For example, isolated cells expressing GLP-1 obtained from germ-free and conventional mice exhibit different transcriptomes, which is rapidly altered after only one day of microbiome colonization, suggesting a more direct effect of the bacteria on the EECs vs. an indirect effect from altered physiology of the germ-free model Further, intestinal expression and circulating levels of gut peptides are altered in germ-free mice , Similarly, HFD converts zebrafish EECs into a nutrient-insensitive state dependent on gut microbiota, as germ-free zebrafish are resistant to the induction of EEC nutrient-insensitivity while an Acinetobacter strain was able to induce EEC nutrient-insensitivity In line with this, bacterial species directly influence GPR, a receptor linked with lipid-induced gut peptide secretion, and GLP-1 expression in vitro Third, LPS, a bacterial byproduct, blunts vagal activation by intestinal nutrients, leptin, or CCK , Thus, there exists a precedent for the ability of small intestinal microbiota to impact nutrient-induced small intestinal gut—brain signaling Fig.

We put forward a working hypothesis for the mechanistic links between small intestinal nutrient-sensing, microbiota, peptide release, and metabolic regulation. Bacterial by-products such as LPS can impair lipid and glucose sensing and potentially disrupt ACSL3 and SGLT1 dependent pathways that regulate glucose and energy homeostasis.

Bile salt hydrolase of bacteria contributes to the bile acid pool and regulates bile acid metabolism. As a result, changes in bile acids can alter GLP-1 release and metabolic regulation via intestinal FXR and TGR5 signaling. High-fat feeding reduces the abundance of small intestinal Lactobacillus species e.

gasseri and consequently inhibits ACSL3 expression and impairs lipid sensing. Lastly, metformin increases the abundance of upper small intestinal Lactobacillus and enhances SGLT1 expression and glucose sensing, while also reducing the abundance of Bacteroides fragilis that results in ileal FXR inhibition and improvement in glucose metabolism.

Bariatric surgery enhances small intestinal nutrient sensing mechanisms and consequently lowers glucose levels, while changes in bile acid metabolism and FXR are necessary for the glucose-lowering effect of bariatric surgery.

In parallel, gut microbiota alters the bile acid pool and thereby potentially affects nutrient sensing and glucose and energy homeostasis. Conjugated bile acids are produced in the liver and released into the duodenum, where they are either absorbed or de-conjugated by the bile salt hydrolase of bacteria.

Bile acids act as signaling molecules in the intestine and elsewhere, binding to FXR and G protein-coupled receptor 19 also known as TGR5 Most, but not all, studies indicate that inhibition of intestinal FXR improves energy and glucose homeostasis , and FXR signaling represses transcription of GLP-1 and inhibits GLP-1 release from L-cells Interestingly, TGR5 signaling increases GLP-1 release from L-cells , thus complicating the role of bile acid signaling in the intestine Fig.

HF-feeding, obesity, and diabetes are all associated with unique microbial profiles in the large intestine.

However, evidence suggests that HF-feeding also alters the composition of small intestinal gut microbiota.

In rodents, the majority of the small intestinal bacteria are Lactobacillius , and HF-feeding results in a drastic reduction in the relative abundance of this genus 45 , Recent work indicates that altered small intestinal microbiota during HFD drives impairments in intestinal lipid-sensing, as the transplant of the small intestinal microbiota of short-term HF fed rats into chow-fed rats abolished the ability of small intestinal lipid infusion to improve glucose tolerance and lower hepatic glucose production.

Treatment of HF-fed rats with a small intestinal infusion of Lactobacillus gasseri enhances upper small intestinal lipid-sensing, via restoration of long-chain acyl-CoA synthetase ACSL3 gasseri exhibits bile salt hydrolase activity and can thus alter the composition of the bile acid pool. Small intestinal L.

gasseri increases ACSL3 and subsequent lipid-sensing through a mechanism dependent on reduced FXR signaling. These findings are consistent with the fact that bile acid sequestrants i.

Recent evidence-based on studies with the anti-diabetic medicine metformin indicate that the glucoregulatory impact of intestinal glucose-sensing is mediated by the small intestinal microbiota.

While metformin directly influences hepatic metabolism , as an orally administered drug metformin concentrations in the small intestine are much greater than in the serum Oral metformin reduces blood glucose levels more than intravenous or portal vein administration , demonstrating a role for intestinal-mediated mechanisms of action in improvements in glucose homeostasis.

Pretreatment of HF-fed rats with metformin restores the ability of upper small intestinal glucose infusion to lower glucose production via increased portal vein GLP-1 levels and small intestinal SGLT-1 expression and in parallel changes the composition of small intestinal microbiota This is in line with several other studies that highlight the importance of the gut microbiota in mediating the beneficial effects of metformin , In addition, individuals with newly diagnosed diabetes treated with metformin for three days exhibit alterations in the gut microbiota including increased Lactobacillus and reduced Bacteroides fragilis abundance, which result in inhibition of FXR signaling to improve glucose metabolism This observation is similar to the ability of L.

gasseri to increase intestinal lipid-sensing to improve glucose homeostasis via FXR 45 Fig. Collectively, these studies highlight small intestinal nutrient-sensing mechanism mediates the beneficial effects of metformin through changes in gut microbiota and bile acids.

Evidence is emerging on the impact of the small intestinal microbiota also in the efficacy of gastric bypass. Despite extensive evidence of an overall role of the large intestinal microbiota in mediating the effects of bariatric surgery , at least one study demonstrated that gastric bypass alters the microbiota of the duodenum, jejunum, and ileum In addition, while the jejunal nutrient-sensing mechanism at least partly mediates the beneficial effects of duodenal—jejunal bypass surgery on glucose homeostasis 98 , the glucose-lowering effect of vertical sleeve gastrectomy is dependent on both the gut microbiota and bile acid signaling Fig.

While technological advancements begin to detail the role of intestinal nutrient-sensing in gut—brain neuronal signaling, they concurrently expand the field. One example of this is the use of single-cell RNA sequencing to understand vagal afferent signaling.

Several groups distinctly labeled nodose ganglion neurons according to their expression profile, however, the results are expansive and sometimes contradictory 44 , Based on these studies, vagal afferent neurons containing GLP-1R have no impact on intestinal nutrient-sensing mechanisms, which are instead regulated by GPRpositive neurons Indeed, various neurons terminating in the intestinal mucosa, that likely sense gut peptides released in response to intestinal nutrients, have no effect on food intake, and only direct activation of a subset of IGLE neurons that detect intestinal stretch and not gut peptides suppresses food intake A subset of EECs called neuropods exist that directly synapse with vagal neurons, and rapidly signal via glutamate to the nucleus of the solitary tract in a single synapse to relay initial spatial and temporal information about the meal that could later be followed by more traditional gut peptide signaling Despite these interesting and exciting advances and the discovery of new nutrient sensory cells, the exact neurons that mediate the gut—brain signaling and nutrient sensing in regulating metabolism are complex and warrant future investigations.

Future studies are needed to start teasing apart these complexities, while also integrating the gut microbiota and metabolites into the picture. For instance, while the gut microbiota can impact EECs, it is plausible that vagal afferents themselves can be impacted by bacterial metabolites In contrast to energy intake, the impact of nutrient-induced gut—brain vagal signaling on energy expenditure has been poorly characterized.

Intestinal lipids regulate brown fat thermogenesis via vagal afferents and possibly via GLP-1R signaling , and vagal knockout of the transcription factor peroxisome proliferator-activated receptor-γ, which is activated by fatty acids and could thus be involved in lipid-sensing, affects thermogenesis Likewise in humans, intraduodenal infusion of intralipid increases resting energy expenditure Nutrient infusions into the duodenum of rats modulate energy expenditure Future work is needed to detail the connections between nutrient-sensing mechanism, gut microbiota, and impact on energy expenditure via thermogenesis in brown or browning white adipose tissue Overall, extensive evidence indicates that targeting nutrient sensing in the small intestine impacts energy and glucose homeostasis during normal physiology and in the context of obesity and type 2 diabetes.

Given the distinct effects of HFD and obesity on the diminution of nutrient-sensing dependent gut—brain pathways, future studies examining the gene and environmental interactions are warranted to further the development of personalized medicine approaches.

Similarly, the expansive role of the gut microbiota in host metabolic health further highlights the need for personalized approaches to treating metabolic diseases. As such, studies in humans and rodents beginning to unravel the interactions between the gut microbiota, small intestinal EECs, and vagal signaling, are laying the groundwork for the development of therapeutics targeting small intestinal nutrient sensing to treat obesity and type 2 diabetes.

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Affiliations 1 University of Florida - Shands Hospital. Introduction The gastrointestinal tract is a highly specialized organ system primarily responsible for nutrient absorption, though it has other roles.

The gastrointestinal tract's wide range of functions include the following: [1] [2] [3] [4] Nutrient absorption - This comes after the breakdown of carbohydrates, proteins, fats, vitamins, and minerals, which are essential for energy production, growth, and cellular maintenance.

Egestion of waste and toxins - The process eliminates indigestible components and harmful substances from the body. Maintenance of hormonal homeostasis - The gastrointestinal tract influences appetite, satiety, and metabolism.

Providing immunity - Immune cells line the gastrointestinal mucosa to defend against pathogens and maintain a balance between tolerance and reactivity.

Influencing behavior - The gastrointestinal tract is a key player in the "gut-brain axis," influencing behavior and cognitive processes.

Cellular Level The Cells of the Gastrointestinal Tract Enterocytes : These are the cells that make up most of the intestinal lining. Development Gastrointestinal development begins during the 3rd week of life. Organ Systems Involved The gastrointestinal system interacts with every organ system.

Nervous System Communication between the nervous and gastrointestinal systems is accomplished by hormonal signals and the enteric nerves. Liver cirrhosis leading to pleural effusion [23]. Function Mouth The mouth is comprised of the lips, teeth, tongue, salivary glands, hard palate, soft palate, uvula, and oropharynx.

It has two natural sphincters: Upper esophageal sphincter: comprised of the cervical esophagus, cricopharyngeus, and inferior pharyngeal constrictor [29]. Lower esophageal sphincter: comprised of the diaphragmatic crura, phrenoesophageal ligament, and intrinsic esophageal muscle fibers [30].

Cardia: the gastric segment that connects with the esophagus. It has a sphincter that prevents gastric contents from refluxing to the esophagus. Fundus: lies inferior to the cardia and functions as residual space for gastric contents.

Body: the largest portion of the stomach and the site where food mixes with gastric acid secretions. Antrum: the inferior portion of the stomach that holds the food-acid mixture before it is moved into the small intestine.

Pyrolus: the portion of the stomach connected to the duodenum. It is comprised of a thick muscular ring that acts as a sphincter controlling gastric emptying.

Of note, the stomach is the first site of absorption for lipid-soluble substances such as alcohol and aspirin. Duodenum: the segment that attaches to the stomach. It is approximately 30 cm or 1 foot long. The duodenum receives the food-acid mixture from the stomach, which then becomes chyme.

Liver, pancreas, and gallbladder secretions come into contact with chyme in this segment, preparing it for further digestion and subsequent absorption.

The duodenum absorbs most of the iron, calcium, phosphorus, magnesium, copper, selenium, thiamin, riboflavin, niacin, biotin, folate, and the fat-soluble vitamins A, D, E, and K. Intestinal villi—the small finger-like projections at the epithelial apices—increase the intestinal cells' surface area for absorption.

Jejunum: measures approximately cm or 8 feet long and is the second portion of the small intestines. The lacteals—the jejunal lymphatic vessels—aid in the absorption of lipids, which have become glycerol and free fatty acids in this segment.

Amino acids are also absorbed in the jejunum, entering the bloodstream through the mesenteric capillaries. Ileum: approximately cm or 5 feet long. It is the most distal segment of the small intestine, terminating at the ileocecal junction.

The ileum absorbs bile salts and acids, ascorbic acid, folate, cobalamin, vitamin D, vitamin K, and magnesium. Mechanism Digestion is the body's natural process of converting food into products that can be absorbed and used for nourishment. This process is unmediated and passively regulated by an electrochemical concentration gradient.

Transcellular pathway: molecules first move from the intestinal lumen into the enterocyte by crossing the apical membrane. From inside the cell, the molecules traverse the basolateral membrane and enter the extracellular space.

In contrast to the paracellular pathway, transcellular transport is active, requiring energy expenditure in the form of Adenosine Triphosphate ATP.

Apical and basolateral enterocyte transporters help facilitate this process. Pathophysiology Carbohydrate Absorption Carbohydrate digestion begins in the oral cavity with the mechanical breakdown of food.

Protein Absorption Chemical protein digestion begins in the stomach and continues into the jejunum. Vitamins and Minerals Vitamins A, D, E, and K are fat-soluble. Clinical Significance Malabsorption occurs when the body cannot effectively absorb nutrients. Review Questions Access free multiple choice questions on this topic.

Comment on this article. Figure Thoracic Lymphatic System. Figure Small Intestinal Villi Schematic Representation. References 1. Sensoy I.

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Paediatr Int Child Health. Digestion begins in the mouth and continues as food travels through the small intestine. Most absorption occurs in the small intestine.

Large food molecules for example, proteins, lipids, nucleic acids, and starches must be broken down into subunits that are small enough to be absorbed by the lining of the alimentary canal. This is accomplished by enzymes through hydrolysis.

The many enzymes involved in chemical digestion are summarized in Table 1. Glucose, galactose, and fructose are the three monosaccharides that are commonly consumed and are readily absorbed. Your bodies do not produce enzymes that can break down most fibrous polysaccharides, such as cellulose.

While indigestible polysaccharides do not provide any nutritional value, they do provide dietary fiber, which helps propel food through the alimentary canal. After amylases break down starch into smaller fragments, the brush border enzyme α-dextrinase starts working on α-dextrin , breaking off one glucose unit at a time.

Three brush border enzymes hydrolyze sucrose, lactose, and maltose into monosaccharides. Sucrase splits sucrose into one molecule of fructose and one molecule of glucose; maltase breaks down maltose and maltotriose into two and three glucose molecules, respectively; and lactase breaks down lactose into one molecule of glucose and one molecule of galactose.

Insufficient lactase can lead to lactose intolerance. Figure 2. Carbohydrates are broken down into their monomers in a series of steps. Proteins are polymers composed of amino acids linked by peptide bonds to form long chains.

Digestion reduces them to their constituent amino acids. You usually consume about 15 to 20 percent of your total calorie intake as protein. The digestion of protein starts in the stomach, where HCl and pepsin break proteins into smaller polypeptides, which then travel to the small intestine.

Chemical digestion in the small intestine is continued by pancreatic enzymes, including chymotrypsin and trypsin, each of which act on specific bonds in amino acid sequences. At the same time, the cells of the brush border secrete enzymes such as aminopeptidase and dipeptidase , which further break down peptide chains.

This results in molecules small enough to enter the bloodstream. Figure 3. The digestion of protein begins in the stomach and is completed in the small intestine. Figure 4.

Proteins are successively broken down into their amino acid components. A healthy diet limits lipid intake to 35 percent of total calorie intake. The most common dietary lipids are triglycerides, which are made up of a glycerol molecule bound to three fatty acid chains.

Small amounts of dietary cholesterol and phospholipids are also consumed. The three lipases responsible for lipid digestion are lingual lipase, gastric lipase, and pancreatic lipase.

However, because the pancreas is the only consequential source of lipase, virtually all lipid digestion occurs in the small intestine. Pancreatic lipase breaks down each triglyceride into two free fatty acids and a monoglyceride.

The fatty acids include both short-chain less than 10 to 12 carbons and long-chain fatty acids. The nucleic acids DNA and RNA are found in most of the foods you eat. Two types of pancreatic nuclease are responsible for their digestion: deoxyribonuclease , which digests DNA, and ribonuclease , which digests RNA.

The nucleotides produced by this digestion are further broken down by two intestinal brush border enzymes nucleosidase and phosphatase into pentoses, phosphates, and nitrogenous bases, which can be absorbed through the alimentary canal wall. The large food molecules that must be broken down into subunits are summarized in Table 2.

The mechanical and digestive processes have one goal: to convert food into molecules small enough to be absorbed by the epithelial cells of the intestinal villi. The absorptive capacity of the alimentary canal is almost endless.

Each day, the alimentary canal processes up to 10 liters of food, liquids, and GI secretions, yet less than one liter enters the large intestine. Almost all ingested food, 80 percent of electrolytes, and 90 percent of water are absorbed in the small intestine.

Although the entire small intestine is involved in the absorption of water and lipids, most absorption of carbohydrates and proteins occurs in the jejunum. Notably, bile salts and vitamin B 12 are absorbed in the terminal ileum. By the time chyme passes from the ileum into the large intestine, it is essentially indigestible food residue mainly plant fibers like cellulose , some water, and millions of bacteria.

Figure 5. Absorption is a complex process, in which nutrients from digested food are harvested. Absorption can occur through five mechanisms: 1 active transport, 2 passive diffusion, 3 facilitated diffusion, 4 co-transport or secondary active transport , and 5 endocytosis.

As you will recall from Chapter 3, active transport refers to the movement of a substance across a cell membrane going from an area of lower concentration to an area of higher concentration up the concentration gradient.

Passive diffusion refers to the movement of substances from an area of higher concentration to an area of lower concentration, while facilitated diffusion refers to the movement of substances from an area of higher to an area of lower concentration using a carrier protein in the cell membrane.

Co-transport uses the movement of one molecule through the membrane from higher to lower concentration to power the movement of another from lower to higher. Finally, endocytosis is a transportation process in which the cell membrane engulfs material.

It requires energy, generally in the form of ATP. Moreover, substances cannot pass between the epithelial cells of the intestinal mucosa because these cells are bound together by tight junctions.

Thus, substances can only enter blood capillaries by passing through the apical surfaces of epithelial cells and into the interstitial fluid. Water-soluble nutrients enter the capillary blood in the villi and travel to the liver via the hepatic portal vein.

In contrast to the water-soluble nutrients, lipid-soluble nutrients can diffuse through the plasma membrane. Once inside the cell, they are packaged for transport via the base of the cell and then enter the lacteals of the villi to be transported by lymphatic vessels to the systemic circulation via the thoracic duct.

The absorption of most nutrients through the mucosa of the intestinal villi requires active transport fueled by ATP. The routes of absorption for each food category are summarized in Table 3. All carbohydrates are absorbed in the form of monosaccharides. The small intestine is highly efficient at this, absorbing monosaccharides at an estimated rate of grams per hour.

All normally digested dietary carbohydrates are absorbed; indigestible fibers are eliminated in the feces. The monosaccharides glucose and galactose are transported into the epithelial cells by common protein carriers via secondary active transport that is, co-transport with sodium ions.

The monosaccharides leave these cells via facilitated diffusion and enter the capillaries through intercellular clefts. The monosaccharide fructose which is in fruit is absorbed and transported by facilitated diffusion alone.

The monosaccharides combine with the transport proteins immediately after the disaccharides are broken down. Active transport mechanisms, primarily in the duodenum and jejunum, absorb most proteins as their breakdown products, amino acids. 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. Despite being hydrophobic, 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.

Until this time, the TCA cycle was seen as a pathway to carbohydrate oxidation only. Most high school textbooks reflect this period of biochemistry knowledge and do not emphasize how the lipid and amino acid degradation pathways converge on the TCA cycle. The cell is depicted as a large blue oval.

A smaller dark blue oval contained inside the cell represents the mitochondrion. The mitochondrion has an outer mitochondrial membrane and within this membrane is a folded inner mitochondrial membrane that surrounds the mitochondrial matrix.

The entry point for glucose is glycolysis, which occurs in the cytoplasm. Glycolysis converts glucose to pyruvate and synthesizes ATP. Pyruvate is transported from the cytoplasm into the mitochondrial matrix. Pyruvate is converted to acetyl-CoA, which enters the tricarboxylic acid TCA cycle.

In the TCA cycle, acetyl-CoA reacts with oxaloacetate and is converted to citrate, which is then converted to isocitrate.

Isocitrate is then converted to alpha-ketoglutarate with the release of CO 2. Then, alpha-ketoglutarate is converted to succinyl-CoA with the release of CO 2. Succinyl-CoA is converted to succinate, which is converted to fumarate, and then to malate. Malate is converted to oxaloacetate. Then, the oxaloacetate can react with another acetyl-CoA molecule and begin the TCA cycle again.

In the TCA cycle, electrons are transferred to NADH and FADH 2 and transported to the electron transport chain ETC.

The ETC is represented by a yellow rectangle along the inner mitochondrial membrane. The ETC results in the synthesis of ATP from ADP and inorganic phosphate P i. Fatty acids are transported from the cytoplasm to the mitochondrial matrix, where they are converted to acyl-CoA.

Acyl-CoA is then converted to acetyl-CoA in beta-oxidation reactions that release electrons that are carried by NADH and FADH 2. These electrons are transported to the electron transport chain ETC where ATP is synthesized.

Amino acids are transported from the cytoplasm to the mitochondrial matrix. Then, the amino acids are broken down in transamination and deamination reactions. The products of these reactions include: pyruvate, acetyl-CoA, oxaloacetate, fumarate, alpha-ketoglutarate, and succinyl-CoA, which enter at specific points during the TCA cycle.

This pathway is known as β-oxidation because the β-carbon atom is oxidized prior to when the bond between carbons β and α is cleaved Figure 6. The four steps of β-oxidation are continuously repeated until the acyl-CoA is entirely oxidized to acetyl-CoA, which then enters the TCA cycle.

In the s, a series of experiments verified that the carbon atoms of fatty acids were the same ones that appeared in the acids of TCA cycle. Holmes, F. Lavoisier and the Chemistry of Life. Madison: University of Wisconsin Press, Krebs, H.

Nobel Prize Lecture org, Kresge, N. ATP synthesis and the binding change mechanism: The work of Paul D. Journal of Biological Chemistry , e18 Lusk, G.

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Advances in Physiological Education 32 , — doi et al. Glucose as the sole metabolic fuel: The possible influence of formal teaching on the establishment of a misconception about the energy-yielding metabolism among Brazilian students.

Biochemistry and Molecular Biology Education 36 , — doi Oliveira, G. Students' misconception about energy yielding metabolism: Glucose as the sole metabolic fuel. Advances in Physiological Education 27 , 97— doi What Is a Cell? Eukaryotic Cells.

Cell Energy and Cell Functions. Photosynthetic Cells. Cell Metabolism. The Two Empires and Three Domains of Life in the Postgenomic Age.

Why Are Cells Powered by Proton Gradients? The Origin of Mitochondria. Mitochondrial Fusion and Division. Beyond Prokaryotes and Eukaryotes : Planctomycetes and Cell Organization.

The Origin of Plastids. The Apicoplast: An Organelle with a Green Past. The Origins of Viruses. Discovery of the Giant Mimivirus.

Volvox, Chlamydomonas, and the Evolution of Multicellularity. Yeast Fermentation and the Making of Beer and Wine.

Dynamic Adaptation of Nutrient Utilization in Humans. Nutrient Utilization in Humans: Metabolism Pathways. An Evolutionary Perspective on Amino Acids. Fatty Acid Molecules: A Role in Cell Signaling. Mitochondria and the Immune Response.

Stem Cells in Plants and Animals. G-Protein-Coupled Receptors, Pancreatic Islets, and Diabetes. Promising Biofuel Resources: Lignocellulose and Algae. The Discovery of Lysosomes and Autophagy. The Mystery of Vitamin C.

The Sliding Filament Theory of Muscle Contraction. Nutrient Utilization in Humans: Metabolism Pathways By: Andrea T. Da Poian, Ph.

Instituto de Bioquimica Medica, Universidade Federal do Rio de Janeiro , Tatiana El-Bacha, Ph. Luz, Ph. Instituto Oswaldo Cruz, Fundacao Oswaldo Cruz © Nature Education. Citation: Da Poian, A. Nature Education 3 9 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. The small intestine is the site of most chemical digestion and almost all absorption. Chemical digestion breaks large food molecules down into their chemical building blocks, which can then be absorbed through the intestinal wall and into the general circulation.

Intestinal brush border enzymes and pancreatic enzymes are responsible for the majority of chemical digestion. The breakdown of fat also requires bile.

Most nutrients are absorbed by transport mechanisms at the apical surface of enterocytes. Exceptions include lipids, fat-soluble vitamins, and most water-soluble vitamins. With the help of bile salts and lecithin, the dietary fats are emulsified to form micelles, which can carry the fat particles to the surface of the enterocytes.

There, the micelles release their fats to diffuse across the cell membrane. The fats are then reassembled into triglycerides and mixed with other lipids and proteins into chylomicrons that can pass into lacteals.

Other absorbed monomers travel from blood capillaries in the villus to the hepatic portal vein and then to the liver. Review Questions. Where does the chemical digestion of starch begin?

Click here to view solutions. Explain the role of bile salts and lecithin in the emulsification of lipids fats. How is vitamin B 12 absorbed? Library Info and Research Help reflibrarian hostos. edu Loans or Fines circ hostos. edu Grand Concourse A Building , Room , Bronx, NY BIO - Human Biology I - Textbook.

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Chapter 20 Chemical Digestion and Absorption: A Closer Look OpenStax , Chemical Digestion and Absorption: A Closer Look. OpenStax CNX. Textbook content produced by OpenStax is licensed under a Creative Commons Attribution License 4. By the end of this section, you will be able to: Identify the locations and primary secretions involved in the chemical digestion of carbohydrates, proteins, lipids, and nucleic acids Compare and contrast absorption of the hydrophilic and hydrophobic nutrients.

Digestion and Absorption. Chemical Digestion Large food molecules for example, proteins, lipids, nucleic acids, and starches must be broken down into subunits that are small enough to be absorbed by the lining of the alimentary canal. Carbohydrate Digestion Flow Chart. Protein Digestion Proteins are polymers composed of amino acids linked by peptide bonds to form long chains.

Digestion of Protein. Figure 3: The digestion of protein begins in the stomach and is completed in the small intestine. Digestion of Protein Flow Chart. Lipid Digestion A healthy diet limits lipid intake to 35 percent of total calorie intake. Nucleic Acid Digestion The nucleic acids DNA and RNA are found in most of the foods you eat.

Table 2: Absorbable Food Substances Source Substance Carbohydrates Monosaccharides: glucose, galactose, and fructose Proteins Single amino acids, dipeptides, and tripeptides Triglycerides Monoacylglycerides, glycerol, and free fatty acids Nucleic acids Pentose sugars, phosphates, and nitrogenous bases.

Absorption The mechanical and digestive processes have one goal: to convert food into molecules small enough to be absorbed by the epithelial cells of the intestinal villi. Digestive Secretions and Absorption of Water. Carbohydrate Absorption All carbohydrates are absorbed in the form of monosaccharides.

Protein Absorption Active transport mechanisms, primarily in the duodenum and jejunum, absorb most proteins as their breakdown products, amino acids.

Lipid Absorption About 95 percent of lipids are absorbed in the small intestine. Lipid Absorption. Nucleic Acid Absorption The products of nucleic acid digestion—pentose sugars, nitrogenous bases, and phosphate ions—are transported by carriers across the villus epithelium via active transport.

Mineral Absorption The electrolytes absorbed by the small intestine are from both GI secretions and ingested foods. Vitamin Absorption The small intestine absorbs the vitamins that occur naturally in food and supplements.

Water Absorption Each day, about nine liters of fluid enter the small intestine. Chapter Review The small intestine is the site of most chemical digestion and almost all absorption.

Review Questions 1. mouth esophagus stomach small intestine. Which of these is involved in the chemical digestion of protein? pancreatic amylase trypsin sucrase pancreatic nuclease. Where are most fat-digesting enzymes produced? small intestine gallbladder liver pancreas. Which of these nutrients is absorbed mainly in the duodenum?

glucose iron sodium water. 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. 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. The small intestine is the site of most chemical digestion and almost all absorption.

Chemical digestion breaks large food molecules down into their chemical building blocks, which can then be absorbed through the intestinal wall and into the general circulation. Intestinal brush border enzymes and pancreatic enzymes are responsible for the majority of chemical digestion.

The breakdown of fat also requires bile. Most nutrients are absorbed by transport mechanisms at the apical surface of enterocytes. Exceptions include lipids, fat-soluble vitamins, and most water-soluble vitamins. With the help of bile salts and lecithin, the dietary fats are emulsified to form micelles, which can carry the fat particles to the surface of the enterocytes.

There, the micelles release their fats to diffuse across the cell membrane. The fats are then reassembled into triglycerides and mixed with other lipids and proteins into chylomicrons that can pass into lacteals.

Other absorbed monomers travel from blood capillaries in the villus to the hepatic portal vein and then to the liver.