Nutrient Absorption in the Gut

Learning Objectives

• Identify the absorption methods for sodium ions, water, carbohydrates, amino acids, lipids, vitamins, and minerals from the gut lumen.
• Understand the physiological importance of having multiple mechanisms for sodium absorption.
• Describe the distinctions between sodium-linked glucose transporters and other glucose transporters.
• Discuss the importance of fatty acid chain length on absorption mechanisms and molecule fate.
• Discuss the importance of peptide and amino acid absorption pathways.
• Understand the basic principles of fat-soluble vitamin absorption, and characteristics of water-soluble vitamin absorption.
• Describe how iron and calcium are absorbed.

Functions of the Digestive System

• The digestive system breaks down food, releases nutrients, and absorbs them.
• These steps are achieved through secretion, motility, digestion, and absorption.
• Digestion is the biochemical breakdown of complex foodstuffs into absorbable units.
• Large food molecules become simple absorbable units during digestion and are propelled forward.
• Absorption transfers absorbable units, water, vitamins, and electrolytes from the digestive tract lumen into the blood or lymph.

Tissue Organization of the Alimentary Canal

• The mucosa lines the alimentary canal.
• The epithelial cell layer of the mucosa is in contact with food or chyme.
• The mucosa physically separates food from the body's inner environment.

Digestive Cells in the Stomach

• Parietal cells produce hydrochloric acid (HCl) and intrinsic factor.
• Chief cells secrete pepsinogen, the inactive proenzyme form of pepsin.
• Enteroendocrine cells secrete hormones, including gastrin (G cells).
• Carbohydrates empty from the stomach fastest, followed by high-protein foods.
• Meals high in triglyceride content stay in the stomach the longest.

Intestinal Adaptations for Absorption

• Villi are small projections from the mucosal lining that increase nutrient absorption surface area.
• Microvilli are hair-like projections that aid in nutrient absorption.

Cells of the Intestinal Lining

• The mucosal epithelial cell layer of the small intestine houses several cell types.
• Enterocytes are absorptive cells.
• The brush border consistes of microvilli-covered cells that express digestive enzymes.
• Goblet cells secrete mucus.
• Crypt cells are epithelial stem cells that replenish dead or sloughed-off cells.

Digestion and Absorption of Nutrients and Water

• A typical daily diet should consist of carbohydrates, proteins, and lipids.
• Most nutrients are consumed as macromolecules.
• Macromolecules must be enzymatically broken down via chemical digestion for absorption.

Nutrient Absorption Mechanisms

• Nutrients are absorbed in different ways, including co-transport (active), facilitated diffusion, osmosis and simple diffusion.

Carbohydrates

• Most dietary carbs are polysaccharides.
• Starch and cellulose come from plant products such as pasta and breads.
• Glycogen comes from animal sources.
• Cellulose, or dietary fiber, is not a substrate for digestive enzymes and cannot be digested.
• Disaccharides include sucrose (sugar) and lactose.
• Monosaccharides, such as glucose and fructose, are absorbable forms of carbs.

Digestion of Carbohydrates

• Polysaccharides are digested by salivary and pancreatic amylase.
• Salivary amylase becomes inactivated by stomach acids.
• Pancreatic amylase continues polysaccharide digestion in the small intestine.
• Amylases reduce starch or glycogen into maltose (a glucose disaccharide) or limit dextrins (short, branched polysaccharides).

Completion of Carbohydrate Digestion

• The digestion of carbohydrates to monosaccharides is completed by brush border enzymes.
• These enzymes are bound to the apical membranes of absorptive cells lining the small intestine.
• Dextrinase and glucoamylase break down limit dextrins and straight-chain glucose polymers into glucose monomers.
• Sucrase hydrolyzes sucrose into glucose and fructose.
• Lactase hydrolyzes lactose into glucose and galactose.
• Maltase hydrolyzes maltose into two glucose molecules.

Absorption of Carbohydrates

• Fructose is absorbed via facilitated diffusion.
• Glucose and galactose enter epithelial cells via active cotransport with sodium.
  • Two sodium ions enter for each glucose transported.
  • Excess sodium is pumped out by the basolateral sodium pump, which requires ATP for energy.
• Sports drinks use the sodium-linked glucose transporter to provide energy to athletes.
• Monosaccharides enter the bloodstream via facilitated diffusion across the basolateral membrane.
• Monosaccharides then travel to the liver for processing.

Protein Digestion

• Proteins must be digested into small peptides and amino acids before absorption.
• To protect secretory cells, digestive enzymes are stored as inactive zymogens.
• Secreted zymogens convert into active enzymes after proteolytic activation.
• Exopeptidases cleave off individual amino acids from one end of a polypeptide.
• Endopeptidases break bonds in the middle of a polypeptide to produce shorter polypeptides.
• Pepsinogen (pepsin) is secreted by chief cells of the stomach.
• Pepsinogen is partially activated by hydrogen ions from parietal cells in the stomach.
• The pancreas secretes zymogens (Trypsinogen and Chymotrypsinogen) into the duodenum.
• The brush border enzyme enterokinase converts trypsinogen to trypsin, which then activates other zymogens.
• Carboxypeptidases and aminopeptidases finish protein digestion.
• Carboxypeptidases and aminopeptidases cleave amino acids from the carboxyl and amino ends of a polypeptide chain, respectively.

Amino Acid and Small Peptide Absorption

• Small peptides and amino acids are actively transported into intestinal epithelial cells by cotransport with ions.
• Amino acids are transported across the basolateral membrane via facilitated diffusion and diffuse into the blood.

Lipid Digestion

• Most dietary lipids (90%) are triglycerides.
• Lipids are hydrophobic and do not mix with stomach contents, making them unreachable by digestive enzymes.
• Bile salts facilitate digestion by emulsifying fat globules into smaller droplets (micelles).
• Bile salts are synthesized by hepatocytes and secreted in the bile.
• Lipases digest lipids, including lingual lipase (saliva and stomach), gastric lipase (gastric lumen), and pancreatic lipase (small intestine).
• Monoglycerides and fatty acids retain their association with bile acids and other lipids to form micelles.

Lipid Metabolism

• Fats with varying fatty acid chain lengths are metabolized differently.
• Long-chain triglycerides (>12 carbons) are very hydrophobic and only digestible when packaged in micelles. Once packaged inside the cell, they are packaged again into chylomicrons and are exocytosed from the basolateral membrane.
• Glycerol, short-chain, and medium-chain triglycerides are relatively water-soluble.
• Glycerol, short-chain, and medium-chain triglycerides enter enterocytes via simple diffusion and take the same path as monosaccharides and amino acids to the blood capillary of a villus.

Absorption of Lipids

• Bile salts from the liver coat fat droplets.
• Pancreatic lipase and colipase break down fats into monoglycerides and fatty acids stored in micelles.
• Monoglycerides and fatty acids move out of micelles and enter cells via diffusion.
• Cholesterol is transported into cells.
• Absorbed fats combine with cholesterol and proteins in the intestinal cells to form chylomicrons.
• Chylomicrons are removed by the lymphatic system.
• Lipid-containing chylomicrons are transported into the lymphatic vessel underlying the epithelial cell layer (lacteal).
• Large numbers of absorbed chylomicrons makes the lymph milky and easy to see in the small intestine.

Key Enzymes and Their Actions

• Amylase, from salivary glands, hydrolyzes polysaccharides to disaccharides.
• Dissacharidases, from small intestine epithelial cells, hydrolyses disaccharides to monosaccharides.
• Pepsin, from stomach chief cells, hydrolyses protein to peptide fragments.
• Trypsin, chymotrypsin and carboxypeptidase, from the exocrine pancreas, attacks different peptide fragments.
• Aminopeptidases, from small intestine epithelial cells, hydrolyses small peptides to amino acids.
• Lipase, from the exocrine pancreas, hydrolyzes triglycerides to fatty acids and monoglycerides.
• Bile salts from the liver, emulsify large fat globules for attack by pancreatic lipase.

Vitamins

• Vitamins are consumed in their absorptive form and do not undergo digestion.
• The mechanism of absorption depends on if the vitamin is hydrophobic or hydrophilic.
• Hydrophobic or fat-soluble vitamins (A, D, E, K) are absorbed with lipids, aided by bile salts.
• Vitamin A, as long-chain fatty acid esters of retinol, must be hydrolyzed into free retinol before absorption.
• Inside the cell, free retinol is re-esterified with long-chain saturated fatty acids and incorporated into chylomicrons for lymphatic absorption
• Water-soluble vitamins are absorbed by active transport or facilitated diffusion.
• Vitamin B12 is absorbed in the ileum only when bound to intrinsic factor, a protein secreted by parietal cells in the stomach.
• Vitamin B12 is necessary for hemoglobin synthesis.
• Deficiency in either B12 or intrinsic factor leads to pernicious anemia.

Minerals

• Mineral absorption usually occurs via active transport.
• 80% of sodium enters the GI tract through secretions, with 20% ingested.
• Sodium absorption varies in different regions of the intestine.
• The leaky epithelium in the duodenum and jejunum absorbs dissolved solutes along with water, due to solvent drag.
• Active sodium transport occurs in the jejunum, ileum, and colon using active mechanism via co-transport and ion pumps.
• Calcium absorption is regulated based on the body’s needs and occurs actively in the duodenum and jejunum.
  • Calcium binds to calcium-binding protein on the brush border and is transported into the cell, and then pumped out by a Ca2+ pump on the basolateral membrane.
  • Calcium absorption is enhanced by 1, 25 (OH) vitamin D3, which increases the amount of calcium-binding protein, and is dependent upon sufficient dietary vitamin D.

Iron

• Iron can be absorbed in both the reduced inorganic form (Fe2+) and when bound to heme.
• Iron is transported across the basolateral membrane into the blood by ferroportin.
• When iron levels are high, the liver secretes hepcidin which inhibits ferroportin, decreasing iron efflux into the circulation.

Water

• Water absorption is passive and driven by an osmotic gradient.
• This is created across the mucosal epithelium through the transport of solutes like sodium from the lumen to the interstitial fluid.
• Water sources include: Drinking water (2L/day) & Secretions from the stomach, intestine, and accessory glands (7L/day).
• Approximately 95% of water is absorbed by the time chyme reaches the colon.

Review of Digestion and Absorption

• Although absorption mostly happens in the small intestine, the stomach does absorb some nonpolar substances, such as alcohol and aspirin.
• Most foods must be enzymatically broken down via chemical digestion for better nutrient absorption
• Polysaccharides (carbs) are digested by amylase, then further digested by brush border enzymes into monosaccharides.
• Fructose is absorbed via facilitated diffusion; glucose and galactose enter epithelial cells via active cotransport.
• Proteins are digested by endopeptidases and exopeptidases, which are released as inactive zymogens.
• Amino acids are actively transported into intestinal epithelial cells.
• Hydrophobic lipids require Bile salts, which emulsify lipids into micelles.
• Lipases digest lipids, where free fatty acids can enter cells via passive diffusion.
• Vitamins are consumed in their absorptive form.
• Fat-soluble vitamins are absorbed with lipids.
• Water-soluble vitamins are absorbed by active transport or facilitated diffusion.
• Mineral absorption usually occurs via active transport.
• Water absorption is driven by the osmotic gradient.