GI Lecture 5 Flashcards
Epithelial cells on villi
The enterocytes that are the cells that take up and deliver into blood virtually all nutrients form the diet.
Lacteal
the lymphatic vessels of the small intestine that absorb digested fats.
Goblet cells of villus
Cell that secretes the main component of mucus
Crypt
A small tubular gland or pit in the small intestinal wall
Villus
Absorptive protrusions of small intestines; increase surface area.
Describe how different molecules are transported across the intestinal epithelium into the blood.
Transcellular rout via carries for large organic molecules (ie amino acids, glucose)
Paracellular route through tight junctions for smaller molecules.
Some molecules transported via both routes.
The number and type of carrier molecules and the structure of the tight junctions varies in different parts of the gut.
What are some dietary sources of carbohydrates
- Sucrose (cane sugar) - a disaccharide of glucose and fructose.
- Lactose (milk sugar) - a disaccharide of glucose and galactose.
- Starches - large polysaccharides in almost all non-animal food
- Glycogen, amylose, alcohol, lactic acid, pectins, dextrins
- Large amounts of cellulose (not digested, fiber)
Describe how amylase breaks down starches
Salivary and pancreatic a‐ amylases partially break down glucose polymers (a-1,4 bonds of amylose and amylopectin) and yield the products: maltose, maltotriose, glucose oligomers and a-limit dextrin a-1,6 bonds and terminal bonds do no break down by amylases.
Is amylase necessary
Salivary amylase is not necessary for healthy humans, but important in infants and pancreatic insufficiency
How is salivary amylase inactivated
By acidic pH levels in the stomach
Isomaltase
The only enzyme that can break down a-1,6 bonds of a-limit dextrins. Yields glucosamylase, sucrase, and isomaltase.
Lactase
A brush border enzyme. Breaks lactose into glucose and galactose before it enters the SGLT-1 channel to transport into cytosol. Especially important for infants
Lactose intolerance
Inability to digest lactose
Where fructose is found
High fructose corn syrups for processed foods
Excess fructose effect
May overwhelm GLUT5 transporter
Sucrase-isomaltase
A brush border enzyme that binds sucrose. Breaks down sucrose into glucose (SGLT-1 transporter) and fructose (GLUT5 transporter) to be sent into cytosol
SGLT1
Na+-glucose transporter - ACTIVE transport - into cytosol
GLUT5
Fructose transporter - into cytosol
GLUT2
Transports glucose, galactose and fructose by FACILITATED diffusion - out of cytosol through basolateral membrane
What happens to sugar molecules that leave the epithelial cell via basolateral membrane
Goes into blood circulation via PORTAL VEIN
In what form are pepsins secreted from the chief cells in the stomach?
Inactive precursor pepsinogens which are inactive in the duodenum at a pH above 5. Pepsins cleave proteins into polypeptides at pH 2-3. 15% of dietary proteins digested this way (but are not necessary).
Where does activation of pancreatic proteases occur
The small intestine brush border, where the enzymes break down proteins into dipeptides or tripeptides (usually not amino acids).
How are peptides absorbed in the small intestine?
By the peptide transporter 1 (PEPT1) together with a proton supplied by an apical Na+-H+ exchanger (NHE).
How are absorbed peptides digested?
By cytosolic proteases, and amino acids are transported into bloodstream by a series of basolateral transport proteins
How are dietary proteins digested into polypeptides and amino acids?
Pepsin
How are polypeptides digested into oligopeptides?
Trypsin, Chymotrypsin, Elastas, Carboxypeptidase A or carbboxypeptidase B
What happens to oligopeptides and amino acids?
Oligopeptides go through brush-border peptidases and become dipeptides and tripeptides; along with amino acids, are finally absorbed.
What are the important dietary lipids?
Neutral fats (triglycerides), phospholipids, plant sterols, and cholesterol
What are some fat soluble vitamins?
Vitamin A (retinoic acid) - regulates gene transcription Vitamin D - important in Ca2+ absorption Vitamin E (tocopherol) - important antioxidant Vitamin K - important in blood clotting
Gastric lipase
has a pH optimum of 4‐ 5.5, it is resistant to pepsin. It acts preferentially to hydrolyze the fatty acid linked to the first position of triglyceride – triglyceride is not fully broken by this enzyme. Fatty acid plus diglyceride.
Pancreatic lipase
Pancreatic lipase acts on both the 1 and 3 positions of the glycerol molecule to liberate esterified fatty acids plus monoglycerides. Neutral pH optimum.
What inhibits gastric and pancreatic lipases
Bile acids
Describe the process of bile acids and colipase
1) Lipase (L) can absorb on the surface of fat droplet.
2) Bile acids displace the
lipase.
3) Colipase binds both bile
acids and lipase. Thus lipase is again close to its substrates in fat droplet.
Phospholipase A2
breaks down dietary phospholipids
Phospholipid -> phospholipase A2 -> lycolecithin + fatty acid
Cholesterol esterase
Degrades cholesterol esters derived from dietary source, and also the esters of vitamin A, D, and E. It can also break down the position 2 in triglycerides.
Cholesterol ester -> cholesterol esterase -> cholesterol + fatty acid
What happens when a large fat aggregate is exposed to bile.
A process called emulsification. The nonpolar portions of bile salts and lecithins intercalate into the lipid, the polar parts remain at the surface. This coating makes the fat droplets easily fragmentable by agitation with the water in small intestine, resulting into smaller and smaller droplets and increased surface area.
What do lipid breakdown products form?
Micelles with bile acids.
Micelle
Surface is covered by bile acids with the hydrophillic part facing out and the hydrophobic part facing in. Micelles transport lipid to the brush border.
What is dependent on micelle formation for transport
Cholesterol, plant sterols and fat soluble vitamins (but not triglycerides and glycerol).
Describe lipid absorption.
When the food bolus is mixed, micelles come into contact with the intestinal brush border. The lipids are absorbed by mostly simple diffusion, but some lipids use specific transporters.
Chylomicron
A droplet of fat present in the blood or lymph after absorption from the small intestine
Apoliopoprotein synthesis and formation of chylomicrons
Apolipoproteins are synthesized in the rough ER and glycosylated, then coated around lipid cores to form chylomicrons. These are secreted from the basolateral side of the enterocyte via exocytosis and they enter to the central lacteal.
What is the general function of vitamins
Cofactors for many metabolic reactions
Fat soluble vitamines
A, D, E, and K - incorporated into miclles and absorbed with lipids. Mechanism unknown.
Water-soluble vitamins
B1, B2, B6, C, biotin, nicotinic acid, pantothenic acid - absorbed by sodium dependent cotransport
Vitamin B12
Cobalamin - forms a complex with the intrinsic factor and this complex binds to a receptor on the ileal cells and is absorbed
Folate
Vitamin B9 - absorbed by at least three different transport mechanisms
Calcium absorption is dependent on …
The presence of the active form of vitamin D. It occurs in all parts of the small intestin.
What are vitamin D supplement examples?
Cholecalciferol = D3 -> converted from 7-dehydroxycholesterol of sunlight, also minor source from fish. Ergocalciferol = D2 (mushrooms, minor source)
Means of making the active form of vitamin D, or 1,25-dihydroxyvitamin D3.
- Either cholecalciferol which is converted from sunlight to this D3 form when absorbed in skin, to the liver, forms 25-hydroxyvitamin D3, to kidney, comes out as active form.
- Minor dietary intake sources (fish and mushrooms) to liver to 25-hydroxyvitamin D3 to kidney to active form.
Role of the active form of vitamin D
Increase calcium absorption in small intestine
Increase urinary calcium reabsorption (kidney)
Increase bone mineralization
Where does most water absorption occur?
The small intestine. Water moves in the intestine passively and is dependent on transport of electrolytes and other solutes.
Compare normal fluid intake to secretions from salivary glands.
Normal fluid intake is 1-2L/day.
6-7L is recieved as secretions from salivary glands, stomach, pancreas, liver, and the small intestine.
Health vs Secretory diarrhea
The absorptive vector
predominates overall in health and most of the fluid used for digestion and absorption is recycled.
Meanwhile in diarrhea, nutrient absorption is largely normal and more water present.
Types of transport mechanisms
- Pumps - active transporters that use energy to move ions against the concentration gradient
- Channels - ions can move passively when the channels are open based on electrochemical gradient
- Carriers - move ions against a concentration gradient by coupling their movement to that of another ion whose transport is favored. Carriers may be either exchangers or cotransporters. They are secondary active transporters.
Sodium-coupled nutrient transport in intestines
Na/K ATPase establishes low intracellular Na+
Glucose transport is coupled to Na+ transport in SGLT1.
Glucose can be moved uphill while Na+ moves downhill. (GLUT 2 transporter separate from Na/K ATPase).
Describe electrogenic Na+ absorption in the colon
No glucose in the colon lumen.
Na+ absorption via epithelial Na channels (ENaC).
K+ absorbed when lumen concentration is high, but it can be secreted if lumen concentration is low.
Describe electroneutral NaCL absorption in the small intestine and colon.
- Na/H exchanger (NHE3) and Cl-/HCO3- (DRA) exchanger transport NaCL into eputhelial cells.
- Na/K ATPase transports Na out
- K/2Cl- transporter KCC1 transports Cl out
Describe how chloride is secreted in the crypts of the small intestine and colon
- Cl initially uptaked by NKCC1 (Na/K/2Cl cotransporter)
- K recycled via K channels
- So Cl- exits via CFTR channels in the crypts (cystic fibrosis transmembrane regulators)
Explain secretory diarrhea, in detail, in terms of regulating chloride secretion by cAMP-dependent agonists
VIP and PGE2 activate adenylate cyclase (A.C.) via Gs protein. This leads to increase of [cAMP] which activates protein kinase A and dissociation of its catalytic subunit (C) from the regulatory subunit (R). CFTR channel is phosporylated and opened and more NKCC1 proteins are added to the membrane.
Cholera toxin activates Gs protein and leads to a huge [cAMP] increase, Cl‐ efflux and watery diarrhea.
How does bicarbonate exit the apical membrane of the epithelial cell back into the intestines.
Either in exchange for Cl supplied by CFTR or via the CFTR channel itself.
How is HCO3- in the cell in the first place
Either produced in the cell from H2O and CO2 using carbonic anhydrase, or taken across basolateral membrane via a sodium bicarbonate cortransporter (NBC1)
Where are sugars and amino acids absorbed?
All small intestine, not colon.
Where are most vitamins absorbed?
In the duodenum and jejunum.
Where are fatty acids absorbed?
Small intestine, not colon
Where are short chain fatty acids absorbed?
Only the colon
Where are bile acids absorbed?
Mainly the ileum
Where is vitamin b12 absorbed?
Only the illeum
Where is sodium absorbed?
Both intestines
Where is K absorbed
Absorbed in small intestines secreted in colon
Where are iron can calcium ions absorbed
Both small intestine only
Where is Cl absorbed
Absorbed AND secreted in both small and large intestines
Where is HCO3- absorbed
Only jejunum, but is secreted in duodenum, illeum, and colon.
