Digestion of Lipids and Vitamins Flashcards
1
Q
villi vs. crypts
A
- absorptive cells are located in vill: removing substances from the lumen
- secretory cells located in crypts: adding substances to the lumen
2
Q
Small intestine
A
Villi (absorptive cells)
crypts (secretory cells)
Columnar epithelial cells
3
Q
Large intestine
A
Surface epithelium (absorptive cells) colonic crypts (gland cells) Columnar epithelial cells
4
Q
Progenitor cells
A
- Found at the base of crypts in both small and large intestine
- Cell turnover is about 48-96 hours and results in cell being sloughed into lumen of intestine
- Cell turnover decreases during starvation and vice versa
5
Q
3 classes of dietary lipids
A
- Triaglycerols (TAGs)
- Phospholipids
- Cholesterol (unesterified)
6
Q
secreted lipids?
A
bile - contains phospholipids (Lecithin and unesterified cholesterol)
- amount secreted usually equals the amount of lipids being absorbed.
7
Q
emulsification
A
process we undergo in order to digest dietary lipids
- formation of oil droplets within water
- accomplished through chewing, gastric chewing, peristalsis, movement between pyloric sphincter and duodenum. With each mechanical process size of oil decreases resulting in an increased SA.
- emulsions are stabilized by a monolayer at the interface formed by dietary and secreted lipids
8
Q
Lipolysis
A
(Digestions of lipids) - accomplished by lipases
- lipases = enzymes responsible for hydrolysis of lipids, present in aqueous lumen at oil-water interfaces.
9
Q
Gastric lipase
A
- only active and stable at pH 4
- resistant to Pepsin
- secreted by Chief cells
- Inactivated by pancreatic proteases in bile salts in small intestine
- cleaves FA’s from TAG’s resulting in one FFA and one diacylglycerol at center of oil droplet.
- medium and short chain GGa’s can move through gastric mucosa
10
Q
Pancreatic lipase
A
- ** major enzyme of lipolysis***
- secreted into duodenum, by acinar cells
- created by pancreas and dependent upon: presence of Colipase, alkaline pH of small intestine, Ca2+, bile salts (allow enzymes to get close to miscelles), fatty acid substrate
Action:
- hydrolyzes all TAG’s
- at oil-water interface - Colipase helps reduce inhibition from phospholipids or proteins on micelle surface
- liberates 2 FFA and liberates 1MAG which moves to the surface of the miscelle
11
Q
Alli and Xenical
A
- drugs that inhibit pancreatic lipase
- most dietary lipids are ingested as TAG’s, which must be degraded into FFA’s and MAG’s by pancreatic enzyme to be taken up….
- this drug results in higher concentration of TAG’s in stools
12
Q
Phospholipiase A2
A
- secreted by pancreas and requires bile salts and alkaline pH
- Action: cleaves one FFA from a glycerophospholipid
- leaves lysophospholipid - no middle fatty acid
13
Q
Carboxyl Ester Hyrdolase
A
- not substrate specific
- hydrolyzes all ester residues, seen in glycerol containing molecules (MAG’s and TAG’s)
- releases free cholesterol and free glycerol
- Action: same action as bile-salt stimulated milk lipase. not active until it hits the duodenum where it is activated by alkaline pH
14
Q
CCK
A
Lipid absorption
- release stimulated by presence of FFA’s in duodenum
- stimulates bile flow into duodenum
- stimulates secretion of pancreatic enzymes: pancreatic lipase and esterases.
15
Q
Lipids in stools
A
- intact acylglycerols are rarely found in stools even in severe malabsorption.
- bacteria likes to digest them, so normally digested by bacteria
- Sudan III staining will show oil droplets that are present in stools.
- short chain and long chain FA’s can be used if patient has problem breaking down long chain FA’s
16
Q
emulsion droplets
A
- larger glycerols in core, smaller glycerols on outside.
- in beginning the vessels can have large arrangment of surface lipids: multilamellar: multiple layers
- as mixing continues the micelle will be formed - micelle contains a lipid monolayer with tails facing the hydrophobic core. results in increased SA and shorter distance for enzymes to reach substrates located in core
- MAGs are hydrolyzed on the surface by lipases and FFA’s released. DAGs and TAGs from the core replace the surface MAGs. the droplet decreases in size, thereby increasing its SA and facilitating more hydrolytic digestion by surface lipases
17
Q
surface components of Micelles
A
cholesterol
MAG’s
lecithins
pancreatic lipases
bile salts (built up around surface, assist in formation of the unilamellar vesicle)
liquid crystalline layer made of bile salts and Ca2+ allows for the micelle formation
18
Q
Core lipids of Micelles
A
DAG’s, TAG’s, cholesterol esters
19
Q
Micelle formation
A
- Increased deposition of the liquid crystalline layer causes budding of multilamellar vesicles from the emulsion droplet.
- Bile salts convert the multilamellar vesicle to unilamellar.
- The addition of more bile salts assists micelle formation.
20
Q
Bulk water phase of lumen
A
where hydrolysis and micelle formation take place
21
Q
mucous gel layer
A
lines the epithelial cells
- created by mucin
- provides a barrier to diffusion by proteins
22
Q
unstirred water layer
A
- it is in disequilibrium with bulk water phase and is right next to the cell membrane
- allows for diffusion of short and medium chain fatty acid monomers directly into enterocytes
- larger FA’s are partitioned back into micelles present
- micelles present maintain high concentration of lipids in unstirred layer because lipids diffuse from micelles into this protonated environment, allowing them to diffuse through the cell membranes
23
Q
enterocyte apical membrane
A
- micelle itself doesn’t diffuse across membrane, therefore lipids must leave micelle.
- Na+/H+ exchangers maintain a protonated microenvironment in unstirred layer
- FA translocates and fatty acid binding proteins enhance translocation and preferentially bind long-chain FA’s which do not easily diffuse.
24
Q
Inside enterocyte: re-esterification process
A
- re-esterification occurs inside the enterocyte in the SER. FFA’s and MAG’s are built back into TAG’s and phospholipids. Fat droplets form in the cisternae of SER.
- apoliprotines are synthesized in RER and trafficked to SER and golgi to assemble the new esterified lipids and to package the lipoprotein particles.
- apolipoproteins encounter TAgs, phospholipids and cholesterol esters in SER and form Chylomicrons and VLDLs
25
Chylomicrons
- the largest lipoprotein made primarily of tags from apolipoproteins
- surface coated with lecithin and phospholipids
26
VLDLs
- very-low-density-lipoprotiens
| - carry mainly endogenous lipids during both fed and fasting states
27
trafficking of Chylomicrons and VLDLs
- Chylomicrons and VLDLs arrive at cis face of golgi apparatus where they are glycosylated.
- Apolipoproteins A-1 associate with the chylomicrons and VLDLs and carry them from trans face to basolateral
27
trafficking of Chylomicrons and VLDLs
- Chylomicrons and VLDLs arrive at cis face of golgi apparatus where they are glycosylated.
- Apolipoproteins A-1 associate with the chylomicrons and VLDLs and carry them from trans face to basolateral
28
how are chylomicrons secreted?
- 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
28
how are chylomicrons secreted?
- 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
29
Water soluble vitamins
- Absorbed in small intestine
- Have specific carriers and/or brush border and luminal enzymes for deconjugation or phosphorylation
- Many Na+ dependent
- Many utilize GPCR and cAMP
30
Fat soluble Vitamins
- Called so because of chemical structure and storage in fat deposits
- Rely on the lipid absorption process because of chemical structure
- Digested from protein haptens by proteolysis of gastric juices
- incorporate into emulsion droplets in small intestine
- Taken up by enterocytes via simple diffusion or through transporters
- Vitamins A,D,E,K
31
What happens when fat soluble vitamins are in enterocyte?
- diffuse into SER. associate with lipid droplets to form chylomicrons or VLDLs. Translate to golgi and translocate into lymph. Once in lymph they enter systemic blood and enter the liver through receptor mediated endocytosis of chylomicrons
32
Malabsorption of lipids and fat-soluble vitamins
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Things that can modulate their absorption rate:
Bariatric surgery
drugs that impair hydrolysis
drugs that impair bile acids
impaired hepatobiliary function
unabsorbable fat substrates
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Treatment: make a water-miscible emulsion of the vitamin
33
Folate deficiency
- water soluble
- deficiency can cause neural tube defects in developing fetus
- results in spina bifida and anencephaly
- women should take folate pills when in pregnancy
34
tetrahydrafolate (THF)
- biochemically active form of Folate, important in synthesis of thymine and purines
- deificiency: results in inhibited DNA synthesis and megaloblastic anemia (where RBC's in bone marrow become large due to uninhibited protein and RNA synthesis)
- treatment: pteroylmonoglutamate (PteGlu1)
35
Digestion of folate
- folate exists in food as PteGlu7 (folate polyglutamate)
- folate conjugase removes glutamate in order to reduce down to PteGlu1
- they are transported into enterocytes by PteGlu1, in the small intestine
36
Pernicious anemia
Vitamin B12 deficiency
- can occur from vegetarian diet
- can be due to no IF secretion
- can occur in elderly due to lack parietal cells due to infection in stomach
- no intrinsic factor due to atrophy or Ab-mediated response against parietal cells - can be due to H.Pylori infection
37
Absorption of Vitamin B12
Vitamin in B12 is bound to proteins in food. Haptocorrin in stomach binds to B12 in stomach. Gastric parietal cells secrete IF which will interact with B12 in the small intestine. The pancreas secretes HCO3-. In small intestine B12 will bind haptocorrin in small intestine and then IF will bind it as well. Ileal enterocyes absorb the IF-B12 complex.
Once in enterocyte CBL-IF will dissociate and it binds transcobalaminII where it exits basolateral membrane into hepatic circulation to the liver. The liver secretes excess CBL into the bile
another name for B12 is Cobalamin (CBL)
38
Pernicious anemia
Vitamin B12 deficiency
- can occur from vegetarian diet
- can be due to no IF secretion
- can occur in elderly due to lack parietal cells due to infection in stomach
39
Schilling test
- tests for IF deficiency
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.
(Presence of radiolabeled vitamin B12 in urine = normal test. Absence of radiolabeled vitamin B12 in urine = abnormal test)
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.
