Intestinal Digestion & Absorption - Prunuske Flashcards
What are the macromolecules that undergo nutrient assimilation?
- Proteins => Peptides/Amino Acids
- Triacylglycerides => Fatty Acids
- packaged into chylomicrons
- Carbohydrates => Monosaccharides (Glucose)
- via amylase
What is “Nutrient Assimilation”?
requires breakdown into monomers or short oligomers
and transport to transverse the Epithelial cell membrane
When are the majority of nutrients absorbed by (time)?
95% of nutrients are absorbed by the time a meal reaches the distal jejunum
What are the Duodenal/jejunum features facilitating digestion and absorption?
- 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
In what three locations does enzymatic hydrolysis of carbohydrates and proteins occur?
- duodenum lumen through pancreatic enzymes
- at the microvillous membrane
- in the enterocytes for peptides
Via what mechanism does carbohydrate assimilation occur?
Intraluminal hydrolysis of polymers (starch, glycogen) by α-amylase (salivary and pancreatic) leads to small di-, tri-saccharides or branched dextrins.
Are amylase blockers (Phaseolus vulgaris white bean extract) an effective weight loss strategy?
- 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
What is Hypolactasia?
- 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
-
Decrease in lactase
What causes the symptoms seen in Hypolactasia?
- 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
What are the two major apical transporters that allow for monosaccharide uptake in the duodenum and jejunum?
SGLT1 – sodium-glucose/galactose cotransporter-1
GLUT5- fructose transporter
How is Glucose and Fructose taken up by the enterocytes?
- 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.
What enzymes are involved in protein digestion?
- 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
- Activate Trypsinogen => Trypsin
- Glycosylated and proline rich proteins are resistant to digestion
Where does amino acid absorption occur?
Occurs in villi of duodenum and jejunum.
How are amino acids digested/absorbed?
- 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
How are peptides absorbed?
- 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.
What is the general overview of Protein Assimilation?
- 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
Why do genetic disorders of apical amino acid transporters not result in amino acid deficiencies?
- 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
- e.g. Hartnup disease: still have oligopeptide cotransporter (PEPT1) to allow Phenylalanine intake if it is bound to another amino acid
How are the majority of lipids digested before reaching the small intestines?
- 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
What form of lipids makes up the majority of our dietary lipids?
- 90% of dietary lipids are triglycerides
- 10% cholesterol, phospholipids, lipid soluble vitamins and toxins
- dense in calories, includes fat soluble vitamins, and add flavor
How does the additional digestion of lipids occur in the small intestines?
- 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
What additional enzymes are produced by the pancreas to help digest lipids?
- 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
Are inhibitors of fat assimilation effective for weight loss?
- 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
How do bile salts contribute to the digestion/absorption of lipids?
- 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.
How do lipids specifically enter enterocytes?
(Hint: 3 ways)
- (1) nonionic diffusion
- (2) collision with the membrane
- (3) carrier mediated transport
How are the chylomicrons absorbed after lipids have been repackaged?
Chylomicrons are taken up by lacteals in the villi and flow with the intestinal lymph through the thoracic lymphatic duct into the venous circulation
What important component of digestion supports the absorption of Vitamin B12 and is made by Parietal cells in the stomach?
Intrinsic Factor
What situations cause an interference with absorption of Vitamin B 12?
Removal of ileum or diabetes drug metformin
What pathologic problems could cause defects in lipid digestion and absorption?
- 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.
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.
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T/F Monosaccharides leave the enterocyte by means of a Na+-coupled transporter protein on the basolateral surface of the cell.
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