Intestinal Digestion & Absorption - Prunuske

Question 1

What are the macromolecules that undergo nutrient assimilation?

Answer 1

• Proteins => Peptides/Amino Acids
• Triacylglycerides => Fatty Acids
  
  • packaged into chylomicrons
• Carbohydrates => Monosaccharides (Glucose)
  
  • via amylase

Question 2

What is “Nutrient Assimilation”?

Answer 2

requires breakdown into monomers or short oligomers
and transport to transverse the Epithelial cell membrane

Question 3

When are the majority of nutrients absorbed by (time)?

Answer 3

95% of nutrients are absorbed by the time a meal reaches the distal jejunum

Question 4

What are the Duodenal/jejunum features facilitating digestion and absorption?

Answer 4

• Plicae circularis in small intestine slows transit of food
• Villi increase surface area
• Segmenting contractions facilitate mixing
• Antimicrobial environment- Brunner’s glands and Paneth cells

Question 5

In what three locations does enzymatic hydrolysis of carbohydrates and proteins occur?

Answer 5

• duodenum lumen through pancreatic enzymes
• at the microvillous membrane
• in the enterocytes for peptides

Question 6

Via what mechanism does carbohydrate assimilation occur?

Answer 6

Intraluminal hydrolysis of polymers (starch, glycogen) by α-amylase (salivary and pancreatic) leads to small di-, tri-saccharides or branched dextrins.

Question 7

Are amylase blockers (Phaseolus vulgaris white bean extract) an effective weight loss strategy?

Answer 7

• Randomized controlled trials generally show no benefits:
  
  • Excess enzyme capacity
  • Starch blockers are proteins that can be digested by pancreatic enzymes
  • Undigested carbohydrates enters large intestine where it can be digested by bacteria leading to bloating and diarrhea

Question 8

What is Hypolactasia?

Answer 8

• Lactose Intolerance
  
  • Decrease in lactase
    
    • normal condition for most of the world’s adult population
  • Secondary after injury to absorptive cells
    
    • due to Crohn’s disease, celiac disease, alcohol

Question 9

What causes the symptoms seen in Hypolactasia?

Answer 9

• Bacterial fermentation of lactose leads to gas accumulation/pain
• Lactic acid production increases osmotic load and water enters the lumen resulting in increased peristalsis and diarrhea

Question 10

What are the two major apical transporters that allow for monosaccharide uptake in the duodenum and jejunum?

Answer 10

SGLT1 – sodium-glucose/galactose cotransporter-1
GLUT5- fructose transporter

Question 11

How is Glucose and Fructose taken up by the enterocytes?

Answer 11

• Glucose (and galactose) are actively taken up through a Na+-monosaccharide symporter, SGLT1 (2 Na+/1 sugar)
  
  • This is a secondary active transport process, critically dependent upon low intracellular Na+ generated by the Na+/K+ pump
• Fructose uptake is promoted by a facilitated transporter, Glut5.
• All monosaccharides leave the basolateral membrane via Glut2 and go to the liver.

Question 12

What enzymes are involved in protein digestion?

Answer 12

• 7 essential amino acids must be obtained from the diet since they can not be synthesized de novo
• Digestion is initiated in the stomach by pepsin (cleaves at neutral aas)
  
  • pepsin is inactive at pH>4.5 (duodenum)
• Pancreatic proteases include endopeptidases and carboxypeptidases that require brush border enzyme enteropeptidase (enterokinase) for activation
  
  • Activate Trypsinogen => Trypsin
    
    • ​Trypsin activates more enzymes
• Glycosylated and proline rich proteins are resistant to digestion

Question 13

Where does amino acid absorption occur?

Answer 13

Occurs in villi of duodenum and jejunum.

Question 14

How are amino acids digested/absorbed?

Answer 14

• Digestion is aided by brush border endo- and exopeptidases generating single amino acids
• Amino acids are transported across the apical membrane by Na+ dependent symporters
  
  • dependent on the basolateral Na+/K+ pump (secondary active transport)
• Many of these enyzmes and transporters are degraded and resynthesized with each meal

Question 15

How are peptides absorbed?

Answer 15

• Peptide transporter 1 PEPT1 cotransports peptides with protons
• Apical sodium/hydrogen exchanger (NHE) supplies the luminal H+ ion
  
  • supported by the basolateral Na+/K+ ATPase.
• Absorbed peptides are further digested by cytosolic proteases.
• Basolateral transporters export surplus amino acids into the blood.

Question 16

What is the general overview of Protein Assimilation?

Answer 16

• Peptides are cotransported with H+
• Amino acids are cotransported with Na+
• For first 6 months, intact proteins are absorbed by endocytosis. Mechanism of passive immunity in infants.
• M cells take up proteins which are transferred to lymphocytes as antigens

Question 17

Why do genetic disorders of apical amino acid transporters not result in amino acid deficiencies?

Answer 17

• If lacking transporter, the body has alternative ways to acquire/produce necessary amino acids
  
  • e.g. Hartnup disease: still have oligopeptide cotransporter (PEPT1) to allow Phenylalanine intake if it is bound to another amino acid
    
    • PEPT1 also facilitates the uptake of many drugs including cephalosporins

Question 18

How are the majority of lipids digested before reaching the small intestines?

Answer 18

• Chewing and churning facilitate emulsification increasing water to oil surface area and reducing surface tension.
• Emulsfied particles are stabilized by coating with bile salts and phospholipids
• Chief cells secrete gastric lipase
  
  • ​​not required but facilitates 10-30% of lipolysis

Question 19

What form of lipids makes up the majority of our dietary lipids?

Answer 19

• 90% of dietary lipids are triglycerides
• 10% cholesterol, phospholipids, lipid soluble vitamins and toxins
• dense in calories, includes fat soluble vitamins, and add flavor

Question 20

How does the additional digestion of lipids occur in the small intestines?

Answer 20

• Free fatty acids in the duodenum trigger the release of CCK that activates pancreatic acinar secretion of lipase and procolipase.
• Pancreatic lipase activity is inhibited by low pH and bile acids prevent lipase binding to fat droplets.
• Colipase is activated by trypsin and binds bile acids recruiting lipase to cleave fatty acids.
  
  • only active in lumen

Question 21

What additional enzymes are produced by the pancreas to help digest lipids?

Answer 21

• Pancreas acinar cells produce additional enzymes that contribute to lipid digestion and many become active in the duodenum which contains higher levels of calcium.
• Cholesterol esterase has broad specificity and can hydrolyze the 2-position fatty acid left untouched by lipase
• Secreted Phospholipase A2 converts phospholipids (cell membranes) into fatty acids and lysophospholipids

Question 22

Are inhibitors of fat assimilation effective for weight loss?

Answer 22

• Orlistat/Xenical pancreatic lipase inhibitor used to treat obesity
  
  • Effect is modest and many patients regain weight if taken off drug
  • Reduces risk of type II diabetes and lowers blood pressure
  • Fatty stool
  • Causes abdominal cramping and diarrhea
  • Inhibit absorption of vitamins A, D, E, K
• Olestra is undigestable fat, too big to be absorbed

Question 23

How do bile salts contribute to the digestion/absorption of lipids?

Answer 23

• Bile salts and phospholipids act to break up (emulsify) large fat globules into droplets.
• Products are taken up by epithelial cell or are “packaged” into small bile salt-coated cylinders called “micelles”.
• Bile salts must be present at a certain minimum level (critical micelle concentration) before micelles will form and fat soluble vitamins must be packaged into micelles for uptake.

Question 24

How do lipids specifically enter enterocytes?

(Hint: 3 ways)

Answer 24

• (1) nonionic diffusion
• (2) collision with the membrane
• (3) carrier mediated transport

Question 25

How are the chylomicrons absorbed after lipids have been repackaged?

Answer 25

Chylomicrons are taken up by lacteals in the villi and flow with the intestinal lymph through the thoracic lymphatic duct into the venous circulation

Question 26

What important component of digestion supports the absorption of Vitamin B12 and is made by Parietal cells in the stomach?

Answer 26

Intrinsic Factor

Question 27

What situations cause an interference with absorption of Vitamin B 12?

Answer 27

Removal of ileum or diabetes drug metformin

Question 28

What pathologic problems could cause defects in lipid digestion and absorption?

Answer 28

• Colipase or lipase deficiency- chronic pancreatitis or congenital mutations (triglycerides only need 10-15% of normal enzyme levels). Treat with pancreatic enzyme supplements
• Zollinger-Ellison excess H+ overwhelms the buffering capacity of bicarbonate in the duodenum. Leading to inactivation of pancreatic lipase (more sensitive to pH than proteases)
• Inadequate bile salt concentrations due to liver dysfunction or outflow of bile leads to emulsification problems.
• Bile uptake defects in the terminal ileum (Crohn’s disease) leads to inadequate bile concentrations.
• Abnormal chylomicron formation (abetalipoproteinemia)
• Abnormal lymphatic transport processes
• Abnormal intestinal motility, short bowel syndrome, or rapid gastric emptying may lead to inadequate time for fat digestion and/or absorption.

Question 29

T/F Amino acids enter enterocytes along with Na+ ions, using five different co-transporters that are selective for neutral, aromatic, imino, positively charged and negatively charged amino acids.

Answer 29

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Question 30

T/F Monosaccharides leave the enterocyte by means of a Na+-coupled transporter protein on the basolateral surface of the cell.

Answer 30

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