Digestion and Absorption of Lipids and Vitamins Flashcards
In the small intestine where are the absorptive cells and secretory cells?
–Villi (absorptive cells) and crypts (secretory cells)
–Columnar epithelial cells
In the large intestine where are the absorptive cells and gland cells?
–Surface epithelium (absorptive cells) and colonic crypts (gland cells)
Where are progenitor cells found?
–Found at the base of crypts in both small and large intestine
Define secretion
Adding substances to the lumen
Define absorption
In adult mammals where are all nutrients absorbed?
removing substances from the lumen
Small intestine absorbs all nutrients
Where are fluids and electrolytes absorbed?
Both in the small and large intestines
What are the three classes of dietary lipids?
- Triacylglycerols (TAG)
- Phospholipids
- Cholesterol
What is the most abundant class of dietary lipids?
TAGs - 90%
Phospolipids comprise only 5% of dietary lipids, what are the major classes?
- Phosphatidylcholine (lecithin)
- Sphingolipid
Cholesterol is a mere 0.5% of dietary lipids, and is primarily what type? What foods contain the other type?
Mostly unesterified cholesterol
esterified cholesterol is only found in liver and blood foods
Emulsification is the formation of oil droplets in water, how it this accomplished?
chewing, gastric churning and intestinal peristalsis between pyloric sphincter and the duodenum.
What are emulsions stabilized by?
a monolayer at the interface formed by dietary and secreted lipids
At what physiological condition is gastric lipase active/stable?
pH 4
Gastric lipase is resistant to pepsin, what is it inactivated by?
Pancreatic proteases in bile salts in the small intestine
What would pancreatic deficiency lead to with regard to gastric lipase?
extended activity into the duodenum
What do mucous neck cells secrete?
Bicarbonate and mucus
What do parietal cells secrete?
Gastric Acid and intrinsic factor
What do enterochromaffin like cells secrete?
Histamine
What do chief cells secrete?
Pepsinogen
Gastric Lipase
What do D cells secrete?
Somatostatin
What do G cells secrete?
Gastrin
What does gastric lipase do? What does this lead to?
Cleaves a fatty acid from TAGs, leading to
one protonated FFA (free fatty acid)
One diacylglycerol
What happens to the protonated FFA that are medium and short chains?
Move into portal blood through gastric mucosa
What factors is pancreatic lipase dependent upon?
- presence of colipase
- alkaline pH of small intestine
- Calcium
- Bile salts
- Fatty acid substrate
What is the action of pancreatic lipase? What is the result?
hydrolyzes all TAGs, resulting in…
2 FFA
1 MAG
What is necessary at the oil-water interface for the action of pancreatic lipase? What does it do?
Colipase, reduces inhibition from phospholipids or proteins on the micelle surface
How do Xenical and Alli (orlistat) work?
Inhibit degradation of triglycerides into FFA and MAGs by inhibiting pancreatic lipase
Pancreatic Phospholipase A2 is secreted as a proenzyme, what is required for its activation? What does it do?
•Requires:
–bile salts
–alkaline pH
•Action:
–Cleaves a FFA from a glycerophospholipid
–Leaves a lysophospholipid
»no middle fatty acid
Phospholipase A2is found in both the small and large intestine. Where does it originate from in the large intestine?
All from bacteria
What does carboxyl ester hyrolase do? This releases?
–Hydrolyzes all esters
–Releases free:
•Cholesterol
•Glycerol
Carboxyl ester hydrolase has the same action as?
•Bile-salt Stimulated Milk Lipase
Where is Bile-salt Stimulated Milk Lipase found?
Describe its stability and activation.
What does it do?
–In human milk for infant fat digestion
–Stable through gastric acidity but not active
–Active at alkaline pH of duodenum and jejunum
–Action:
»Hydrolyzes:
•DAGs, MAGs, TAGs, fatty esters
Cholecystokinin (CCK) is important in lipid absorption, what stimulates its release? What does it stimulate?
- Release stimulated by free fatty acids in duodenum
- stimulates…
- Bile flow into duodenum
- secretion of pancreatic enzymes
- Pancreatic lipase
- Pancreatic esterase
Lipids are rarely found in stools, even in severe cases of malabsorption, why is this?
What test is performed to detect fat in stool samples?
Due to bacterial digestion in the colon
Sudan III staining
Medium-chain fatty acids are absorbed independently of micelles or bile salts, what happens to them once inside of the enterocyte?
What are these important for?
- Transferred directly into blood
- Important fat substitute for patients with related malabsorption
Emulsion droplets absorb products and components of lipid digestion. They are multilamellar until budding of mixed micelles. What types can be found?
•multilamellar-
–multiple lipid bilayers
•unilamellar-
–one lipid bilayer
•micelle-
–lipid monolayer with tails facing the hydrophobic core
What are the surface components of an emulsion droplet?
–cholesterol
–MAGs
–lecithins
–pancreatic lipases
–bile salts
•Built up around surface, assist in formation of the unilamellar vesicle
–Liquid crystalline layer made of bile salts, surface components and Ca2+ rich fatty soaps.
What are the core lipids of an emulsion droplet?
–DAGs
–TAGs
–cholesterol esters
What is the process by which emulsion droplets are broken down?
- MAGs are hydrolyzed on the surface by lipases and free fatty acids are released.
- DAGs and TAGs from the core replace the surface MAGs.
- The droplet decreases in size, thereby increasing its surface area and facilitating more hydrolytic digestion by surface lipases.
–Increased deposition of the liquid crystalline layer causes budding of multilamellar vesicles from the emulsion droplet.
How are multilamellar vesicles converted to unilamellar?
Bile salts convert the multilamellar vesicle to unilamellar
What are the microclimates of the intestine?
- Bulk water phase of the lumen - where hydrolysis and micelle formation take place
- Mucous gel layer - lines epithelial surface and provides a barrier to diffusion by proteins called mucins
- Unstirred water layer
The unstirred water layer is juxtaposed to cell membranes and in disequilibrium with bulk water phase due to mucous gel. What does this layer allow for?
Diffusion of short and medium chain fatty acid monomers directly into enterocytes.
Micelles present in the unstirred water layer maintain high concentrations of lipids. Why?
Because lipids diffuse from micelles in this protonated environment.
What maintains the protonated environment in the unstirred layer?
Na/H+ exchangers
In the enterocyte apical membrane, fatty acid translocases and fatty acid binding proteins enhance translocation and preferentially bind what?
long-chain fatty acids which do not easily diffuse
Inside the enterocyte, re-esterification is performed where?
Smooth endoplasmic reticulum - SER: long chain FA’s are assembled back into TAGs and phospholipids
In the enterocyte, where are the apolipoproteins synthesized? Where are they trafficked to?
Synthesized in the RER
trafficked to SER
In the SER, apolipoproteins encounter TAGS, phospholipids and cholesterol esters in SER and form?
- Chylomicrons
- Very-low-density lipoproteins (VLDLs)
Describe the size, composition and surface coating of chylomicrons.
–The largest lipoprotein made primarily of TAGs
–Surface coated with lecithin and phospholipids
What do VLDLs carry?
–Carry mainly endogenous lipids during both fed and fasting states
Where do vesicles from the SER carry chylomicrons and VLDLs to?
The golgi cis face
What associates with chylomicrons and VLDLs in the golgi apparatus?
•Apolipoprotein A-I associates with them here
After glycosylation of Apolipoproteins occurs in the golgi apparatus, where do the vesicles take chylomicrons and VLDLs?
From the golgi trans face to the basolateral membrane
Describe the passage of secreted chylomicrons and VLDLs through the lymphatic system.
- Secreted chylomicrons and VLDLs enter lymph through lymphatic capillaries (They are too large to pass through fenestrae)
- Through lymph capillaries they enter the cisternae chyli
- Through the cisternae chyli they enter the thoracic duct
- Through the thoracic duct they enter the blood via the left subclavian vein
Water Soluble Vitaminsare absorbed in small intestine, and have specific carriers and/or brush border and luminal enzymes for deconjugation or phosphorylation. What are they dependent upon? What do they utilize?
–Many Na+ dependent
–Many utilize GPCR and cAMP
Fat-soluble Vitamins are named so because of chemical structure and storage in fat deposits. They rely on the lipid absorption process due to chemical structure.
How are they digested from protein carriers?
How are they taken up by enterocytes?
- Digested from protein carriers by proteolysis of gastric juices
- incorporate into emulsion droplets in small intestine
- Taken up by enterocytes via simple diffusion or through transporters
What happens to fat soluble vitamins once inside the enterocyte?
–Diffuse to SER
•Can occur through specific carrier proteins
–Ex. Retinol-binding protein
–Associate with lipid droplets to form chylomicrons or VLDLs
–Translocate to Golgi
–Translocate into lymph
What happens to fat soluble vitamins once in the lymph?
–Enter systemic blood
–Enter the liver through receptor mediated endocytosis of chylomicrons
What can fat soluble vitamin deficiencies arise from?
How do we treat?
–Can occur from malabsorption
•Bariatric surgery
•drugs that impair hydrolysis
•drugs that impair bile acids
•impaired hepatobiliary function
•unabsorbable fat substrates
Treat with water miscible emulsions
What can a folate deficiency lead to in a developing fetus?
–Deficiency can cause neural tube defects in developing fetus
•Spina bifida and anencephaly
What does a deficiency in tetrahyrdafolate (THF) result in?
•Inhibited DNA synthesis
•Megaloblastic Anemia
–Red blood cells in bone marrow become large due to uninhibited protein and RNA synthesis
How is THF deficiency treated?
•pteroylmonoglutamate (PteGlu1)
How does folate exist in food? What removes the glutamate residues to PteGlu1?
–Folate exists in food as folate polyglutamate (PteGlu7)
–Folate conjugase
In the small intestine PteGlu1 is transported into enterocytes, by what structure is this accomplished?
What happens to it in the liver?
PteGlu1 carrier
Enzymatically changed to THF
Vitamin B12 is only synthesized by?
Microbes found in animal products
Vitamin B12 is a coenzyme that transfers a methyl group onto homocysteine to create what?
Methionine
Methionine is an essential aa, what does the body use during deficiency of methionine?
Intracellular stores of folate
What do folate and B12 deficiencies cause?
Cause same megaloblastic anemia
Vitamin B12 is released from protein carriers in the stomach via pepsin and low pH. What are they bound by in the stomach?
haptocorrin
By what other name is B12 known?
Cobalamin
Where does intrinsic factor interact with cobalamin? What causes this interaction to begin?
When they reach the small intestine.
–HCO-3 secreted by pancreas induces release of cobalamin from haptocorrin, allowing cobalamin to bind IF
Cobalamin-IF binds receptors on apical surface of enterocytes in ileum, once in the enterocyte, cobalamin and IF dissociate. What does cobalamin bind next and why?
–Binds transcobalamin II
•Required for basolateral exit
Cobalamin is delivered through hepatic circulation to liver which does what with excess cobalamin?
The liver secretes excess cobalamin into bile
What are five causes of B12 deficiency?
- Vegetarian diet
- Pernicious anemia
- metabolization by bacteria of small intestine
- Crohn disease
- Ileal resection
What is pernicious anemia caused by in the elderly?
•in elderly, caused by lack of parietal cells
–can be due to atrophy or Ab-mediated immune response against parietal cells or IF
–no IF secretion
–no absorption without IF
What test is used to detect IF deficiency?
Schilling test
What are the four stages of the Schilling test?
•Stage 1:
–Oral Radioactive B12 taken, intramuscular injection of nonradioactive B12 given to block storage in liver.
–24 hr urine sample collected. If abnormal proceed.
•Stage 2:
–Both repeated with oral Intrinsic Factor.
•Stage 3:
–Both repeated with antibiotics to rule out GI bacteria cause of deficiency.
•Stage 4:
–Both repeated with pancreatic enzymes to rule out pancreatitis.
