Nutrients and Digestion PDF

Page 1062 26.4 Nutrients and Their Digestion The term essential nutrients indicates substances that must constitute part of the diet for survival. The six essential nutrients are carbohydrates, proteins, lipids, minerals, vitamins, and water. These nutrients and their functions in the body are descr...

Page 1062 26.4 Nutrients and Their Digestion The term essential nutrients indicates substances that must constitute part of the diet for survival. The six essential nutrients are carbohydrates, proteins, lipids, minerals, vitamins, and water. These nutrients and their functions in the body are described in depth in sections 27.1 through 27.3. This section discusses the chemical digestion of the foods that we eat. In addition to the mechanism of their breakdown, we describe their absorption and general use by the body. We describe the breakdown of macromolecule essential nutrients including carbohydrates, lipids, and proteins, as well as nucleic acids, the last of which is not an essential nutrient. All are digested by the process of hydrolysis, the breaking of chemical bonds with an accompanying addition of a water molecule (see section 2.7a). A summary of the chemical digestion of each of the categories of macromolecules is presented in at the end of section 26.4. table 26.2, 26.4a Carbohydrate Digestion LEARNING OBJECTIVES 33. Name the three classes of carbohydrates. 34. Explain the processing in the oral cavity that initiates carbohydrate digestion and how it is completed in the small intestine. Carbohydrates are organized based upon the number of repeating units of simple sugars. You learned in section 2.7c that carbohydrates may be classified as monosaccharides (e.g., glucose, fructose, galactose), disaccharides (e.g., sucrose, maltose, lactose), and polysaccharides (e.g., starch, cellulose). Chemical digestion of carbohydrates consists of (a) the breakdown of starch into individual glucose molecules and (b) the breakdown of disaccharides into the individual monosaccharides that compose them. The oral cavity and small intestine are the main sites of carbohydrate digestion. Carbohydrate Breakdown in the Oral Cavity Digestion of starch begins in the oral cavity. It is catalyzed by salivary amylase that is synthesized and released from the salivary glands (see section 26.2b). Salivary amylase breaks the chemical bonds between glucose molecules, within the starch molecule, to partially digest the starch molecule. The extent of starch digestion is dependent upon the length of time the salivary amylase is allowed to act on the starch. Salivary amylase is inactivated by the low pH of the stomach when the bolus is swallowed. This inactivation typically occurs within 15 to 20 minutes after the bolus enters the stomach. The larger the meal, the longer salivary amylase remains active. This extended activity occurs because it takes longer for the swallowed bolus to be mixed with the low pH of the gastric juices that inactivate the salivary amylase. This is more likely when the bolus is within the fundus of the stomach, where smooth muscle contractions are the weakest and the pH is the highest. No new enzymes for carbohydrate digestion are introduced in the stomach. Carbohydrate Breakdown in the Small Intestine Starch digestion continues within the small intestine. Please refer to figure 26.26 as you read this section and and note that each of the indicated steps is illustrated in this figure. Pancreatic amylase, which is produced and secreted from the pancreas into the small intestine (step 1), continues the digestion of starch into shorter strands of glucose (5 to 25 glucose molecules, oligosaccharides), maltose (disaccharide of two glucose molecules), and individual glucose molecules (step 2). Figure 26.26 Carbohydrate Digestion in the Small Intestine. (a) Pancreatic amylase is produced by the pancreas and secreted into the small intestine. (b) Pancreatic amylase continues digestion of starch that began in the oral cavity by salivary amylase, and brush border enzymes complete the breakdown of starch to individual glucose molecules. (c) Lactose and sucrose disaccharides are each digested by a specific brush border enzyme. Watch Video: Enzyme Action and the Hydrolysis of Sucrose The completion of starch breakdown is accomplished by brush border enzymes embedded within the epithelial lining of the small intestine (step 3). These enzymes include dextrinase and glucoamylase, which break the bonds between glucose subunits of oligosaccharides, and maltase that breaks the bond between the two glucose molecules that compose maltose ( figure 26.26b). The digestion of other ingested disaccharides, such as lactose (milk sugar) and sucrose (table sugar), requires only one enzyme each. Each enzyme is specifically named for the substrate it digests. Lactase digests lactose to glucose and galactose, and sucrase digests sucrose to glucose and fructose ( figure 26.26c). These enzymes are brush border enzymes. Individuals with either a reduced amount or a lack of lactase enzyme are referred to as being lactose intolerant (see Clinical View 3.2: “Lactose Intolerance”). The monosaccharides released from these enzymatic reactions include glucose, fructose, and galactose. They are absorbed in the small intestine across the epithelial lining into the blood (see figure 26.16c). All venous blood from the small intestine is transported through the hepatic portal vein to the liver, where fructose and galactose will be converted into glucose. Glucose has different fates. It can become part of the blood glucose, be taken up by any cell to be oxidized through cellular respiration (see section 3.4), be taken up by liver cells and muscle cells and synthesized into glycogen and stored (see section 2.7c), or be converted into fat (triglycerides) and stored in adipose connective tissue. Cellulose is a carbohydrate that is a component of plant cell walls. Cellulose is not chemically digested because we lack the enzymes re-quired to break the bonds between its glucose molecules. Thus, cellulose, along with other indigestible substances, is fiber that adds “bulk” to the contents within the lumen and facilitates its moving through the GI tract. A summary of carbohydrate digestion is included in table 26.2. Page 1063 INTEGRATE CLINICAL VIEW 26.16 Celiac Disease (Gluten-Sensitive Enteropathy) Celiac disease (also known as sprue or gluten-sensitive enter-opathy) is an autoimmune disorder that affects up to 1% of the population in the United States. Gluten—a protein common in wheat, rye, and barley (but not rice or corn)—stimulates an immune response in affected individuals that damages the villi of the small intestine, which interferes with absorption. Common foods that contain gluten include breads, pizza, pasta, and many processed foods. Symptoms include abdominal pain, bloating, and chronic diarrhea, which leads to nutrient deficiencies because of malabsorption. Although there is no cure for celiac disease, it can be effectively managed by following a gluten-free diet. Recent research indicates the some humans who are infected with a reovirus (which usually cause mild or no symptoms) may develop celiac disease as a result of the virus triggering intestinal changes that lead to gluten intolerance. Mark Steinmetz WHAT DID YOU LEARN? 25 What enzyme is released from the salivary glands to begin the break down starch? What enzyme is released from the pancreas into the small intestine to continue the breakdown of starch? 26.4b Protein Digestion LEARNING OBJECTIVES 35. Explain why the proteolytic enzymes of the stomach and pancreas are synthesized in inactive forms. 36. Describe the activation and role of pepsin in the initiation of protein digestion in the stomach. 37. Describe the activation of proteolytic enzymes and the chemical digestion of proteins that occurs in the small intestine. Proteins are polymers composed of amino acid subunits linked by peptide bonds (see section 2.7e). Digestion of protein releases individual amino acids so that the amino acids may be absorbed into the blood and transported to cells for the synthesis of new proteins (see section 4.8b). Proteins are broken down into amino acids by enzymes that target peptide bonds between either specific adjacent amino acids within the protein or any amino acid from the end of a protein. All enzymes that digest protein, collectively called proteolytic enzymes or proteases, are released from both the stomach and pancreas as inactive enzymes. These enzymes must be activated (e.g., pepsinogen is activated to pepsin within the low pH of the stomach). This is because the proteolytic enzymes would destroy the proteins within the cells that produce them and, in the case of protein-digesting enzymes produced in the pancreas, would destroy the cells lining the main and accessory pancreatic ducts as they passed through those ducts. Protein Breakdown in the Stomach Protein digestion begins within the stomach lumen. Hydrochloric acid that is formed from parietal cells (see figure 26.12) causes a low pH within the stomach that both denatures proteins to facilitate their chemical breakdown and activates the formation of pepsin from pepsinogen (as described in section 26.2d). Pepsin is a proteolytic enzyme that chemically digests proteins into shorter strands of amino acids (e.g., oligopeptides). Chyme is moved from the stomach into the small intestine before proteins are completely digested to amino acids. Page 1064 Protein Breakdown in the Small Intestine The high pH of the small intestine inhibits further action by pepsin on protein shortly following the entry of chyme into the small intestine. Please refer to figure 26.27 as you read this section and and note that each of the indicated steps is illustrated in this figure. Three of the enzymes that continue the digestion of protein are synthesized and released from the pancreas into the small intestine in inactive forms—trypsinogen, chymotrypsinogen, and procarboxypeptidase (step 1). Once these inactive forms of the enzymes reach the small intestine, trypsinogen is activated by the enzyme enteropeptidase (en′tĕr-ō-pep′ti-dās; previously called enterokinase), an enzyme previously synthesized by the small intestine and released into the lumen of the small intestine (step 2). Enteropeptidase activates trypsinogen to trypsin. Trypsin in turn activates additional molecules of trypsinogen to trypsin, as well as chymotrypsinogen to chymotrypsin (kī-mō-trip′sin) and procarboxypeptidase to carboxypeptidase (kar-bok′sē-pep′ti-dās). Figure 26.27 Protein Digestion in the Small Intestine. (a) Pancreatic enzymes for protein digestion are produced and secreted into the small intestine in an inactive form. After reaching the small intestine, these enzymes are activated. (b) The locations where different proteindigesting enzymes break peptide bonds are highlighted in purple. Trypsin and chymotrypsin break the bonds between specific amino acids within the protein to produce smaller strands of amino acids called peptides (step 3). (Trypsin cleaves a protein specifically at positively charged amino acids of arginine and lysine, whereas chymotrypsin cleaves specifically at hydrophobic amino acids, including phenylalanine, tryptophan, and tyrosine; see figure 2.25, which shows the 20 different amino acids.) Carboxypeptidase is restricted to breaking the bond only between an amino acid on the carboxyl end and the remaining protein (it releases one amino acid at a time). Dipeptides and free amino acids are the breakdown products of carboxypeptidase. The brush border enzyme dipeptidase breaks the final peptide bond between the two amino acids of a dipeptide to release two amino acids and the brush border enzyme aminopeptidase generates free amino acids from the amino end of peptides (step 4). Amino acids are then absorbed across the small intestine epithelial lining and enter into the blood. Amino acids can be used as building blocks of new proteins by cells, or if excess amino acids are absorbed, they are either (a) converted into glucose (by gluconeogenesis in the liver primarily or kidney) or (b) deaminated (amine [—NH2] group is removed in the liver) and used as fuel for cellular respiration (see digestion is included in table 26.2. section 27.6c). A summary of protein WHAT DID YOU LEARN? 26 How are proteolytic enzymes activated in the stomach and in the small intestine? Explain why this is necessary. Page 1065 26.4c Lipid Digestion LEARNING OBJECTIVES 38. Explain the role of bile salts in mechanical digestion of lipids and the role of pancreatic lipase in the chemical digestion of triglycerides. 39. Discuss the process by which lipids are absorbed. Lipids are highly variable structures that contain different arrangements of their building blocks (see section 2.7b). Lipids have one unifying property, which is that they are not water-soluble (they are hydrophobic). Two major ingested lipids are triglycerides (or neutral fats) and cholesterol. Triglycerides are composed of three fatty acids bonded to a glycerol molecule, and enzymes are required to break the bonds between glycerol and fatty acids. Chemical digestion of cholesterol is not required for its absorption. Lipid Breakdown in the Stomach Lingual lipase (produced by intrinsic salivary glands in the mouth; see section 26.2b) is a component of saliva in the oral cavity. The optimal pH of this enzyme (4.5 to 5.4), however, means it is not activated until it reaches the stomach. Once in the stomach, triglycerides undergo limited digestion by both lingual lipase and gastric lipase (an enzyme produced by chief cells of the stomach; see section 26.2d). These “acidic lipases” digest approximately 30% of the triglycerides to diglyceride and a fatty acid. Neither of these lipase enzymes requires the participation of bile salts. Lipid Breakdown in the Small Intestine Triglyceride digestion continues within the small intestine. The processing of lipids that occurs in the small intestine is facilitated by mechanical digestion that occurs through bile. Please refer to figure 26.28 as you read this section and and note that each of the indicated steps is illustrated in this figure. Lipids are hydrophobic molecules and do not dissolve in the luminal fluids of the digestive system, but rather form relatively large lipid masses. For example, when butter is added to water, the butter does not mix with the water but remains separate. Thus, the large lipid droplets must first be mechanically separated into smaller droplets before chemical digestion by pancreatic lipase can effectively occur. This process of mechanical digestion is called emulsification (ē-mŭl-si-f ĭ-kā′shun). (This is similar to breaking an ice cube into ice chips.) Emulsification occurs by the action of bile salts, which are part of bile. Bile is produced by the liver and stored, concentrated, and released from the gallbladder. Bile salts are amphipathic molecules composed of a polar head and a nonpolar tail. The nonpolar tails position themselves around the lipid droplets with the polar heads next to the aqueous fluid in the lumen (like an inverted spiked ball with the lipid droplets in the center; step 1). This structure is called a micelle (mi-sel′, mī-sel; micella = small morsel). Thus, the function of bile salts is to emulsify lipids so that pancreatic lipase, which is produced and secreted from the pancreas into the small intestine, has greater “access” to the triglyceride molecules and may more effectively chemically digest the triglyceride molecules. (Note that the process of emulsification is facilitated by lecithin, which is a type of phospholipid molecule within bile.) Figure 26.28 Lipid Digestion and Absorption in the Small Intestine. Bile salts emulsify lipids within the small intestine, forming micelles to facilitate fat digestion by pancreatic lipase. After the pancreatic lipase has digested the triglyceride, the monoglycerides and the fatty acids are taken into an epithelial cell, where triglycerides are re-formed, then wrapped along with other lipids within protein to form a chylomicron. Chylomicrons are released from vesicles within the epithelial cells by exocytosis and then enter a lacteal within the lamina propria of the small intestine wall. Watch Video: Small Intestine Digestion Page 1066 Each triglyceride is chemically digested by pancreatic lipase into a monoglyceride and two free fatty acids (step 2). No brush border enzymes are required in the breakdown of triglycerides. A summary of lipid (i.e., triglyceride) digestion is included in table 26.2. Table 26.2 Digestion of Macromolecules Location Carbohydrates Proteins Lipids Nucleic Acids Oral cavity Starch—salivary No protein digestion Lingual lipase No nucleic acid (saliva) amylase⟶ partially added but digestion digested starch activated in low pH of stomach Stomach No additional Protein—pepsin⟶ Triglyceride— No nucleic acid (gastric enzymes added polypeptide and lingual lipase⟶ digestion peptide fragments monoglyceride juice) and fatty acids (limited amounts) Triglyceride— gastric lipase⟶ monoglyceride and fatty acids (limited amounts) Small Partially digested Protein—trypsin⟶ Triglyceride— DNA— intestine starch—pancreatic polypeptide and pancreatic deoxyribonuclease⟶ (pancreatic amylase⟶ peptide fragments lipase⟶ deoxyribonucleotides juice secreted oligosaccharides, Protein— monoglyceride RNA—ribonuclease⟶ into maltose, and chymotrypsin⟶ and fatty acids ribonucleotides duodenum) glucose polypeptide and (within micelles) peptide fragments Protein— carboxypeptidase ⟶ amino acids from carboxy end of peptides Small Oligosaccharides— Dipeptides— No brush border Nucleotides— intestine dextrinase and dipeptidase⟶ amino enzymes required phosphatase⟶ (brush glucoamylase⟶ acids for completing nucleosides and lipid digestion phosphate maltose, glucose Location Carbohydrates Proteins border Maltose—maltase⟶ Peptides— Nucleosides— enzymes) glucose aminopeptidase⟶ nucleosidase⟶ Lactose—lactase⟶ amino acids from nitrogenous base and glucose, galactose amino end of sugar (ribose or Sucrose—sucrase⟶ peptides deoxyribose) glucose, fructose Lipids Nucleic Acids Lipid Absorption Lipids, because they are hydrophobic molecules, require specialized steps for their absorption. Two important structures associated with lipid absorption are: micelles and chylomicrons. Micelles Micelles, which were just described, are within the lumen of the small intestine (step 1). These structures contain digested triglycerides (monoglycerides and free fatty acids), cholesterol, other lipids (e.g., lecithin), and fat-soluble vitamins (vitamins A, D, E, and K) enclosed within bile salts. Micelles transport lipids to the simple columnar epithelial lining of the small intestine. Here, the lipids enter the epithelial cells by simple diffusion, whereas the bile salts remain in the small intestine lumen (step 3). Eventually, in the last portion of the ileum, bile salts are recovered from the GI tract back into the blood by active transport and ultimately recycled to the liver for reuse. New bile salts are synthesized by hepatocytes to replace those inevitably lost during elimination of feces. Chylomicrons Chylomicrons (kī′lō-mī′kron; chylos = juice, micros = small), in comparison, are formed within the epithelial cells lining the small intestine (step 4). Within these cells, fatty acids are reattached to the monoglyceride to re-form triglycerides. Triglycerides, cholesterol, and other lipid molecules are then “wrapped” with protein to form a chylomicron. The Golgi apparatus (see section 4.6a) packages chylomicrons into secretory vesicles. Vesicles containing chylomicrons merge with the plasma membrane of epithelial cells to release chylomicrons by exocytosis (see section 4.3c). Chylomicrons are too large to pass through blood capillary walls but instead enter the lacteals, the lymphatic capillaries of the small intestine. The overlapping endothelial cells of the lacteals act as one-way valves to permit entry of chylomicrons (step 4). Page 1067 INTEGRATE LEARNING STRATEGY 26.4 Lipid digestion presents challenges in the “handling” of these hydrophobic molecules. They are handled differently within the lumen of the small intestine and the epithelial cells of the intestinal wall: Within lumen: Bile salts separate blobs of lipid into smaller blobs by mechanical digestion to form micelles. Within micelles, pancreatic lipase chemically digests triglycerides. Within epithelial cells: Triglycerides are reassembled and protein wraps the triglycerides and other lipids (e.g., cholesterol) to form chylomicrons, which are then absorbed into the lymphatic capillaries and transported by the lymph to enter the blood. INTEGRATE CLINICAL VIEW 26.17 Cystic Fibrosis and the Pancreas An overview of cystic fibrosis (CF) and its effects on the respiratory system was provided in Clinical View 23.1: “Cystic Fibrosis.” The thick mucus associated with CF that blocks the respiratory passageways also blocks the pancreatic ducts. This blockage prevents pancreatic juice containing both digestive enzymes and HCO3− from reaching the duodenum. Two primary unfavorable events result: (a) Pancreatic juices accumulate in the pancreas causing destruction of the acini (exocrine gland cells), which often leads to pancreatitis (inflammation of the pancreas) with progressive fibrosis (replacement of pancreatic tissue with scar tissue), and (b) impaired chemical digestion within the duodenum with decreased absorption of nutrients (see section 26.4e). This leads to malnutrition and poor growth and development. The lack of amino acid absorption results in decreased protein synthesis, including protein synthesis by the liver, which produces plasma proteins such as albumin (see section 27.6c). Recall from section 20.3 that a decrease in plasma proteins decreases colloid osmotic pressure (COP), which results in edema (see figure 25.5). Because of this malnourishment, CF patients are advised to take pancreatic enzymes; follow a high-energy, high-fat diet; and take supplemental vitamins. Recall from section 21.1b that all lymph enters the blood, via either the right lymphatic duct or the thoracic duct, at the junction of the internal jugular vein and the subclavian vein. Chylomicrons enter the blood and deliver lipids to the liver and other tissues (e.g., adipose connective tissue, skeletal muscle tissue, cardiac muscle; see section 27.6b). WHAT DID YOU LEARN? 27 What is the function of bile salts in lipid digestion? Is this considered chemical digestion or mechanical digestion? 28 How do micelles and chylomicrons function in lipid digestion? 26.4d Nucleic Acid Digestion LEARNING OBJECTIVE 40. Describe the digestion of nucleic acids. Nucleic acids are polymers of nucleotides. The two types of nucleic acid polymers are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). A nucleotide monomer is composed of three components: sugar (either deoxyribose or ribose), a phosphate group, and a nitrogenous base (see section 2.7d). Recall that nucleic acids are not an essential nutrient, but like essential nutrients, they are digested by specific enzymes of the digestive system. Nucleic Acid Breakdown in the Small Intestine Nucleic acid digestion occurs in the small intestine. The nucleases (deoxyribonuclease and ribonuclease), synthesized and released by the pancreas, begin the digestion of nucleic acids. Each breaks the phosphodiester bond between the individual nucleotides of DNA and RNA, respectively. Nucleotides are the products: deoxyribonucleotides from DNA and ribonucleotides from RNA. The breakdown of the nucleotides is accomplished by brush border enzymes embedded in the epithelial lining of the small intestine. These enzymes include (a) phosphatase, which breaks the bond holding the phosphate to the rest of the nucleotide (without the phosphate, this molecule is called a nucleoside), and (b) nucleosidase, which breaks the bond between the sugar and the nitrogenous base of the nucleoside, releasing the sugar and nitrogenous base. All nucleic acid component building blocks are absorbed across the epithelium of the small intestine into the blood. These include phosphate, the sugar (ribose or deoxyribose), and the nitrogenous bases (thymine, adenine, guanine, cytosine, and uracil). Table 26.2 summarizes nucleic acid digestion. A visual summary of the digestive processes of macromolecule essential nutrients is presented in figure 26.29. Page 1068 Page 1069 INTEGRATE CONCEPT OVERVIEW Figure 26.29 Nutrients and Their Digestion. Chemical digestion of nutrients (a) begins in oral cavity assisted by salivary gland secretions and (b) continues within the stomach. Digestion in the small intestine is facilitated by (c) accessory digestive organ secretions, which are released into the duodenum. (d) The small intestine is the site for the majority of both chemical digestion and absorption of nutrients. The final changes to the chyme occur within (e) the large intestine, where further changes to chyme involve the intestinal microbiota and feces are formed. (Digestion of nucleic acids is not shown.) APR Module 12: Digestive: Animations: Digestive System Overview WHAT DID YOU LEARN? 29 Where does nucleic acid digestion occur? 26.4e Water, Electrolyte, and Vitamin Absorption LEARNING OBJECTIVES 41. Describe the absorption of water, electrolytes, and vitamins. 42. Explain the details of vitamin B12 absorption. The small intestine absorbs digested biological macromolecules as described in the previous sections. It is also the component of the GI tract where most water, electrolytes, and vitamins are absorbed. Water Absorption The amount of water that enters the small intestine daily is approximately 8–9 liters. Ingested water accounts for about 2.3 L (see figure 25.4), but most of the water (about 6.7 L) is contributed by secretions of the digestive system (saliva, gastric secretions, bile, pancreatic juice, intestinal secretions). Our small intestine functions to absorb almost all of the water (about 6–7 L) that enters the small intestine. Thus, the daily water content of chyme entering the large intestine is only about 2 liters. The large intestine will then absorb about 1.8 liters, which leaves, on average, only about 0.2 liter (or 200 mL) of water lost daily in the feces (which contributes a relatively small amount to water output; see figure 25.4). Water is absorbed across the epithelial lining of the small and large intestines into the blood capillaries by osmosis (see section 4.3b). Blood is transported throughout the body; as it moves through blood capillaries, water leaves the blood to enter the interstitial cells and systemic cells to help maintain fluid balance (see figure 25.3a). Electrolyte Absorption Electrolytes were first described in section 2.4c, and their function in fluid and electrolyte balance is discussed in section 25.3. Electrolytes enter the GI tract through ingestion and as components of accessory digestive gland secretions. (Dietary sources of these substances are listed in table 27.2.) Our small intestine functions to absorb almost all of the electrolytes that enter the small intestine. Most electrolyte absorption is unregulated and is, instead, dependent upon the amount in the diet. The greater the amount ingested, the greater the amount absorbed. (Blood levels are normally maintained because excess amounts are typically eliminated in the urine; see section 24.6e.) Diarrhea (e.g., caused by food poisoning, gastroenteritis, laxatives, medications) leads to an excessive loss of both water and K+, with the associated risk of hypokalemia (see section 25.3b). Diarrhea (with the loss of HCO3−) can also result in metabolic acidosis (see Clinical View 25.7: “How Does Vomiting or Diarrhea Alter Blood H+ Concentration?”). Iron is unusual in that its absorption is controlled. The hormone hepcidin is released from the liver in response to iron levels (see table 17.2). Hepcidin inhibits the transport protein (ferroportin) located in the epithelial (basolateral) membrane of the GI tract. Thus, when iron levels are low, hepcidin release is decreased, which removes this inhibition, allowing for greater iron absorption. Vitamin Absorption Vitamins are organic molecules that are categorized as either (a) fat-soluble vitamins or (b) water-soluble vitamins (see section 27.3a). Fat-soluble vitamins (A, D, E, and K) are absorbed from the small intestine lumen into epithelial cells with lipids within micelles (see section 26.4c). Note that fat-soluble vitamins require lipid for their absorption—without it, the fat-soluble vitamins are not absorbed, continue through the GI tract, and are lost in the feces. This is a concern for individuals with insufficient fat in their diet, who may not be absorbing sufficient levels of fat-soluble vitamins. Water-soluble vitamins (B and C) are absorbed through various membrane transport mechanisms, including simple diffusion and active transport. Vitamin B12, because of its large molecular size, must be transported by receptor-mediated endocytosis (see section 4.3c). The process requires intrinsic factor, which is released from parietal cells of the stomach (see section 26.2d). Intrinsic factor is a glycoprotein that, following its formation by parietal cells, continues within the GI tract lumen, ultimately reaching the distal portion of the ileum. The intrinsic factor, during its transport from the stomach to the ileum, binds vitamin B12 that is within the chyme to form a B12–intrinsic factor complex. (Think of intrinsic factor as like a ball of Velcro that rolls through the lumen of the GI tract from the stomach to the ileum binding vitamin B12 along the way.) It is within the distal ileum that these complexes bind to receptors on the epithelial cell lining and are taken up by receptor-mediated endocytosis. The lack of intrinsic factor (e.g., from a gastric bypass; see Clinical View 26.4: “Gastric Bypass”) prevents the binding and absorption of the vitamin B12 that is required for erythrocyte formation, resulting in the development of pernicious anemia (see Clinical View 18.2: “Anemia”). WHAT DID YOU LEARN? 30 Explain the details of vitamin B12 absorption.