Macronutrient Digestion

Macronutrient Digestion

• Hydrolysis of carbohydrates requires H₂O
• General reaction for carbohydrate hydrolysis: R"-R' + H2O -> R"OH + R'H
• Hydrolysis of lipids generally involves triglycerides (TG)
• Triglyceride hydrolysis releases 3 free fatty acids (FFA) and glycerol at the brush border
• Hydrolysis of proteins/peptides is also a key part of macronutrient digestion

Carbohydrate Digestion

• Amylases are the primary enzymes involved
• Saliva (α-amylase) is inhibited by the acidic environment in the stomach
• Pancreatic amylase is more active
• It is predominately duodenal and generates maltose

Intestinal Formation of Monosaccharides

• Four key enzymes for this process: lactase, sucrase, maltase, and α-dextrinase
• These are produced from enterocytes and act at the brush border
• Lactose is broken down into fructose + glucose
• Sucrose is broken down into fructose + glucose
• Absorption happens into the intestinal epithelium
• Transport occurs across the basolateral surface
• Monosaccharides enter the circulation through the portal vein and are directed immediately to the liver

Digestion of Proteins

• Connective tissues must be digested to release the content of animal tissue
• Collagen is digested by pepsin, which is a collagenase that functions best at a pH of 2-3
• Elastin undergoes a two-step conversion: Proelastase -> Elastase
• Polypeptides are generated, and peptidases such as aminopolypeptidase & dipeptidase in the enterocytes of the Brush Border
• About 2-3 AA polypeptides are absorbed
• Intracellular peptidases release AA during absorption

Digestion of Fats

• Lipases are a large family of fat-metabolizing enzymes
• Pancreatic lipase involves hydrolysis, requires H2O, and functions at a neutral pH
• Bile and agitation emulsify fats.
• The enzyme is released in the duodenum
• Most absorption happens in the upper small intestine
• The enzymes act at the surface of the droplet

Anatomical Basis of Absorption

• Normal absorption involves about 1.5L of intake and 7L of GI secretions, totaling 8-9L
• Surface epithelium is maximized by Kerckring folds, intestinal villi, and brush border
• The brush border consists of the surface of villi and fingerlike projections, enriched in transport enzymes
• Total absorptive epithelium has ~1000X surface of intestinal length & circumference, estimated at 250 sq m

Absorption in Small Intestine

• Capacity is in excess of average daily intake (5-10 fold depending on the macronutrient)
• Active transport of Na+ drives secondary active transport for other ions, glucose, & AA
• Water absorption is driven by osmosis, passive & bidirectional
• Water moves transcellularly and paracellularly and is stimulated by aldosterone
• Colon is the most active area for water absorption

Chloride & Bicarbonate

• Chloride absorption follows an electrochemical gradient
• It drive secretion of bicarbonate, which is important for digestion.
• Bicarb is reabsorbed via formation of carbonic acid and free diffusion of CO2 back across the epithelium
• Extreme secretion causes diarrhea because active secretion of ions causes water to follow, can be stimulated by bacteria or Cholera Toxin

Other Key Ions

• Calcium is absorbed in the duodenum and stimulated by PTH & VitD
• Iron is absorbed using Transferrin, which is secreted by the liver into bile and then internalized by the Transferrin Receptor
• K+, Mg2+, PO4 absorption is active
• Monovalent ions are absorbed more than Bivalent ions

Monosaccharides

• CHO must be converted to monosaccharides for absorption
• Absorption involves active and passive processes and it is generally active at the apical and passive at the basolateral membrane
• Circulation and insulin action maintains gradient at basolateral surface
• SGLT1 is not equal to SGLT2

Peptides & AA

• Absorption involves secondary active transport
• Tripeptides, dipeptides, and AA are absorbed using 10+ transporters
• Transporters can be neutral or charged (anionic vs. cationic)
• Classified under the SLC Class of transporters

Fat Absorption

• Lipases generate FFA (free fatty acids) which freely diffuse across BBM (brush border membrane)
• Esterification occurs in the enterocyte by Acyl CoA Synthetases (fatty acid trapping)
• Reticular Enzymes MGAT and DGAT generate TGs
• TGs are packaged in very large vesicles in the Golgi
• Occurs through lymphatic transport
• It is too large to enter portal circulation and bypasses the liver, being directed to the arterial circulation

Colonic Absorption & Excretion

• Potential for large loss of water & electrolytes due to gastric secretions
• The large intestine contributes to active recovery of ions and Osmotic reabsorption of water
• Microbial metabolism occurs and contributes to generation of Vit K & B12, Thiamine, Riboflavin, Methane, and SCFA
• Faces are 30% dead bacteria, 10-20% inorganic matter, 30% insoluble fiber, 5-10% fat, and 2-3% protein