Digestion and Absorption

Parotid Gland

Secretes alpha-amylase, beginning the carbohydrate digestion in mouth.

Pancreatic Amylase

Performs most of the carbohydrate digestion in SI lumen

Pancreatic Enzymes

Secretion is stimulated by CCK

Carbohydrate Digestion

SI lumen digests into di-, tri-, or oligosaccharides, not monosaccharides 

Apical Membrane Hydrolase

Produced by enterocytes, which digest nutrients directly at the surface of these absorbing epithelial cells (membrane-associated enzymes)

Integral membrane proteins that digest carbs and peptides

Brush Border Enzymes

Hydrolyze disaccharides (maltose, sucrose, lactose), maltotriose, oligosaccharides to monosaccharides

Absorption of Monosaccharides

1. Na+/K+ ATPase removes Na+ from cell into the blood

2. Na+ Glucose symporter into cell (due to decreased Na+ in the cell)

3. Glucose moves down the concentration gradient into the blood

4. 100% absorbed by end of jejunum

Pepsin

Formed from pepsinogen reaction with HCl in the stomach lumen

Trypsin

Formed from the trypsinogen reaction with enteropeptidase, then causes activation of other enzymes to digest peptides.

Protein Digestion Enzymes

1. Chymotrypsinogen → Chymotrypsin

2. Proelastase → Elastase

3. Procarboxypeptidase A → Carboxypeptidase A

4. Procarboxypeptidase B → Carboxypeptidase B

5. All formed from trypsin 

Pancreas Protein Digestion

1. Protenases (trypsiogen, chymotrypsinogen, etc.) are packaged in the pancreas as inactive precursors to protect the pancreas

2. Activation occurs in the small intestine, where other enterokinases activate trypsin, which then activates proteinases. 

Membrane Associated Peptidases

Aminopolypeptidases

Carboxypeptidases

Dipeptidases

Tripeptidases 

Cytoplasmic peptidase generating single AA absorbed di- or tri-peptidases

Protein Digestion

Cut different peptide bonds occurring in the cell surface, cytoplasm, or by enzymes secreted from the pancreas.

Absorption of AA

1. Use Na+/K+ ATPase to set up a concentration gradient

2. Co-transport systems using sodium (for AA) or hydrogen (for dipeptides and tripeptides) ion gradients into cell

3. Primary active transport (for some AA)

4. Passive diffusion via transporters into blood

5. 100% absorbed by the end of the jejunum 

Dietary Fats

Supply 40% of daily calories with 90-95% being from triglycerides (triacylglycerols)

Provide fat soluble vitamins (D, A, K, E)

Issue with Fats

Not water soluble, but the gut lumen is an aqueous environment, causing difficulties with absorption

Solution for Fat Absorption

Increase solubility of fats by mixing with detergents (bile)

Function of Liver

1. Synthesis of bile salts

2. Carb/lipid/protein metabolism

3. Synthesis of plasma proteins (albumins, globulins, and proteins required for blood clots)

4. Processing of drugs and hormones

5. Detoxification

6. Storage of excess nutrients

Bile Salts

Used in the small intestine for the emulsification and absorption of lipids

Amphipathic (hydrophobic and hydrophilic)

Bile

Mix of bile salts, lecithin (phospholipid), cholesterol, bilirubin (RBC breakdown waste)

Synthesized in liver 

Stored and concentrated in gallbladder

Gallbladder

Concentrated bile by absorption of NaCl

Regulated release of bile through CCK

CCK

Regulates the release of bile by stimulating gallbladder contraction and opening the sphincter of Oddi

Produce enzymes from pancreatic acinar cells

Bile Acids

Derived from cholesterol, which is hydrophobic

Formation of Bile Salt

Bile acid conjugated to the amino group of glycine or taurine rendering bile acid amphipathic 

Bile Salt Lifecycle Steps

1. Primary bile acid (liver synthesis)

2. Primary Bile Salt (primary bile acid with glycine or taurine conjugated by liver)

3. Secondary Bile Acid (bacteria remove conjugate and hydroxyl) → secreted to duodenum and encounter intestinal bacteria

4. Secondary Bile Salt (liver re-conjugates with glycine or taurine) → returned to liver

Primary Bile Acid

What liver synthesizes

Primary Bile Salt

Primary bile acid with glycine or taurine conjugated by liver

Secondary Bile Acid

Bacteria remove conjugate AND hydroxyl, which is secreted to duodenum and encounter intestinal bacteria

Secondary Bile Salt

Liver re-conjugated with glycine or taurine, which is returned to liver

Enterohepatic Circulation

Bile salts released in the duodenum and then absorbed in the terminal ileum

Bile Secretion in Liver

1. Hepatocytes secrete bile components

2. Secreted into canaliculi

3. Stored in gallbladder to be concentrated

Bile Canaliculi

Microscopic channels located within the liver that play a crucial role in bile secretion and transport. Disposal route for the liver to dump unwanted materials.

Color of Bile

Conjugation of bilirubin makes it water-soluble and yellow, which is then excreted in bile to the gut lumen.

Colonic bacteria bile and have it excreted

Stomach Lipid Digesiton

No chemical digestion but chruning/mixing reduces size of large lipid droplets

Small Intestine Lipid Absorption

Bile salts emulsify fat droplets working with lipase to generate micelles

Colipase

Remove inhibitory effect of bile salts on lipase

Produced and secreted by pancreatic acinar cells in the pancreas

Pancreatic Lipase

Inhibited by bile salts

Micelles

Water soluble transport vesicles formed by bile salts and lecithin surronding food-derived lipids. 

Lipids diffuse into epithelial cells of SI, allowing for free FAs to be TAGs and with other lipids and lipoproteins make chylomicrons 

Chylomicrons

Large lipoprotein particles that transport dietary fats and cholesterol from SI epithelium to the lacteals of the lymphatic system.

Absorption of Water Soluble Vitamins

Absorbed primarily in the small intestine through carrier mediated transport systems

Vitamin B12

Absorption requires additional proteins, such as intrinsic factor, which is produced by parietal cells in the stomach

Also uses haptocorrin (R)

Salt Absorption

GI tract fluid release and absorption with small intestine and large intestine absorbing 9L of fluid daily (water and electrolyte)

Sodium Absorption in Intestines

1. Sodium-coupled nutrient absorption (SI)

2. Electroneutral NaCl absorption (SI and Colon)

3. Electrogenic Na+ absorption (Colon)

Sodium Absorption in SI

Sodium-coupled nutrient absorption is exemplified by the uptake of glucose from the intestinal lumen

Sodium-glucose transporter 1 cotransports Na+ and glucose into cell

Elector-neutral Absorption of NaCl

Enters across the apical membrane via the coupled activity of a sodium/hydrogen exchanger (NHE) and a chloride/bicarbonate exchanger (DRA).

Route of basolateral chloride exit via the potassium/2 chloride cotransporter (KCC1) remains speculative)

Electroneutral Absorption

Na⁺ and Cl⁻ are absorbed together in a way that no net charge is moved across the epithelium.

1. Na⁺/H⁺ exchanger (NHE3)

• On the apical membrane

• Brings Na⁺ in, sends H⁺ out

2. Cl⁻/HCO₃⁻ exchanger (DRA or PAT-1)

• Also on the apical side

• Brings Cl⁻ in, sends HCO₃⁻ out

3. Cl-/K+ Cotransporter (2 Cl- and 1 K+ into blood)

4. Na/K+ ATPase moves 3 Na+ out

Electrogenic Sodium Absorption

Occurs in the colon with sodium entering epithelial cells via epithelium sodium channels (ENaC)

Epithelial Sodium Channels (ENaC)

Na+ moved into the cell in the colon 

Moved into blood via Na+/K+ ATPase

Water Absorption

Water follows NaCl due to osmosis, occurring in small and large intestine

Dietary Minerals

Chemical elements required by living organisms

Fully dependent on dietary intake because the body cannot synthesize them (Calcium, iron)

Bioavailability of Calcium

Tight binding to organic anions such as oxalate making them in absorbable

Plants are rich in the organic anions that hinder the absorption of Ca2+ 

Calcium Absroption

1. Active transcellular transport → active even when [Ca2+] is low

2. Activated by vitamin D

3. Passive paracellular transport → active only when [Ca2+] is high

Calbindin

Protein that binds to Ca2+ keeping cytosolic free Ca2+ low and delivers substrate to efflux transporters

Sites of Calcium Absorption

Duodenum only site where transcellular active absorption

Paracellular transport occurs in duodenum to colon

Active Vitamin D

Increases Ca2+ absorption in the small intestine by increasing the expression of proteins involved in absorption

Iron Bioavailability

Total amount of iron in the idet is poor predictor of iron uptake

Meat (20-25% absorbed)

Animal and plant sources (3-10% absorbed)

Regulation of Iron Absorption

Absorptive enterocytes are major site regulating iron balance because body is poor at excreting iron

Iron-induced liver protein (hepcidin) inhibits iron absorption by affecting FPN1

Hepicidin

Inhibits iron absorption by impacting FPN1

Large Intestine

Indigestible waste, unabsorbed bile and fluid enter

Functions to reabsorb water, salt, and some minerals

Formation of solid feces

Propels waste for shitting

Large Intestine Bacteria

Bacteria accumulate due to low motility

Prevent pathogenic bacterial growth

Breakdown dietary fiber (produce gas)

Synthesize vitamin K

Haustral Contractions/Segmentation

Contractions of the large intestine that churn chyme to aid in water and electrolyte absorption

1 in 30 minutes

Mass Movement

Contractions of large segments of the colon at a rate of 3-4 times per day, driving feces to rectum

Triggered by gastrocolic reflex (increasing room for food)

Defecation Reflex

Rectum filled with feces causes the SM wall of the rectum to contract, with the internal anal sphincter relaxing (involuntary control of SMC). 

Voluntary contorl of external anal sphincter (skeletal) relaxed to release contents

Iron Absorption

1. Iron reduced from ferric (Fe3+) to ferrous (Fe2+) by DcytB (ferric reductase)

2. Iron enters cell through DMT1

3. Stored in the cell with ferritin (if body is full of iron)

4. Exported into the blood through hephaestin (Fe2+ → Fe3+ allowing binding to transferrin

FPN1

Ferroprotein 1, export protein of iron

Ferritin

Iron storage is lost when body stores are filled, lost when enterocyte is sloughed into the lumen

Hephaestin

Transfers Fe2+ into Fe3+ allowing for iron to bind transferrin (export in the blood)