digestion and absorption of lipids

Question 1

Types of cholesterol

Answer 1

esterified cholesterol only found in liver and blood foods; unesterified cholesterol in everything else

Question 2

emulsification

Answer 2

Formation of oil droplets in water

Question 3

How does emulsification happen?

Answer 3

Chewing, gastric churning, intestinal peristalsis between pyloric sphincter and duodenum
With each mechanical process size of oil droplet decreases
With decrease in size comes increase in surface area

Question 4

How are emulsions stabilized?

Answer 4

Emulsions are stabilized by a monolayer at the interface formed by dietary and secreted lipids.

Question 5

Lipases

Answer 5

Enzymes responsible for hydrolysis of lipids

Present in aqueous lumen at oil-water interfaces

Question 6

Gastric lipase- when active? resistance/ inactivation?

Answer 6

Only active and stable at approx. pH 4
Resistant to Pepsin
Inactivated by Pancreatic Proteases in bile salts in small intestine
(Pancreatic deficiency would result in extended activity into duodenum)

Question 7

gastric lipase action

Answer 7

Cleaves a fatty acid from TAGs
Results in:
- one protonated FFA (free fatty acid) 
                 (Those that are medium and short chain move into portal blood through gastric mucosa)
- one diacylglycerol

Question 8

pancreatic lipase- where secreted, what dependent upon?

Answer 8

Major lypolytic enzyme of pancreatic secretions
Secreted into duodenum
Secreted in huge excess
Dependent on:
Presence of Colipase, Alkaline pH of small intestine, Calcium, Bile Salts, Fatty acid substrate

Question 9

Action of pancreatic lipase

Answer 9

At Oil-Water interface
colipase necessary here to reduce inhibition from phospholipids or proteins on micelle surface
Hydrolyze all TAGs
Results in:
2 FFA
1 MAG

Question 10

dietary lipids

Answer 10

Most dietary lipids are ingested as triglycerides

Must be degraded into FFA and MAGs to be taken up

Question 11

Xenical and Alli (orlistat)

Answer 11

inhibit degradation of lipids by inhibiting Pancreatic Lipase.

Question 12

Phospholipase A2

Answer 12

Pancreatic-Secreted as proenzyme
Requires: bile salts, alkaline pH
Action: Cleaves a FFA from a glycerophospholipid, Leaves a lysophospholipid , no middle fatty acid

In small intestine

In large intestine all from bacteria

Question 13

Carboxyl Ester Hydrolase

Answer 13

Not substrate specific
Hydrolyzes all esters
Releases free: Cholesterol, Glycerol
Same action as bile-salt stimulated milk lipase

Question 14

Bile-salt Stimulated Milk Lipase

Answer 14

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

Question 15

CCK

Answer 15

Stimulated release by free fatty acids in duodenum
Stimulates bile flow into duodenum
Stimulates secretion of pancreatic enzymes
pancreatic lipase
pancreatic esterase

Question 16

Lipids in stools

Answer 16

Intact acylglycerols rarely found in stools
Even in severe cases of malabsorption
Due to bacterial digestion in colon
Sudan III Staining
Chemical test for stool fat

Question 17

How are medium chain fatty acids absorbed?

Answer 17

Medium-chain fatty acids are absorbed independently of micelles or bile salts
Once inside the enterocyte they are directly transferred into blood
Important fat substitute for patients with related malabsorption

Question 18

Emulsion Droplets

Answer 18

Absorb products and components of lipid digestion

Multilamellar until budding of mixed micelles.

Question 19

Multilamellar

Answer 19

multiple lipid bilayers

Question 20

unilamellar

Answer 20

one lipid bilayer

Question 21

micelle

Answer 21

lipid monolayer with tails facing the hydrophobic core

Question 22

Surface components of emulsion droplets

Answer 22

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.

Question 23

core lipids of emulsion droplets

Answer 23

undigested lipids:
DAGs
TAGs
cholesterol esters

Question 24

What happens to emulsion droplets as they move through digestion

Answer 24

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.

Question 25

Micelle formation

Answer 25

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.

Question 26

Microclimates of the intestine

Answer 26

bulk water layer mucous gel layer unstirred water layer enterocyte apical membrane

Question 27

Bulk water phase of the lumen

Answer 27

where hydrolysis and micelle formation take place

Question 28

Mucous gel layer

Answer 28

lines the epithelial surface | provides a barrier to diffusion by proteins called mucins

Question 29

Unstirred water layer

Answer 29

juxtaposed to cell membranes in disequilibrium with bulk water phase due to mucous gel allows for diffusion of short and medium chain fatty acid monomers directly into enterocytes larger fatty acids are partitioned back into micelles present micelles present maintain high concentrations of lipids in unstirred layer because lipids diffuse from micelles in this protonated environment

Question 30

enterocyte apical membrane

Answer 30

micelles do not diffuse across membrane therefore lipids must leave micelle Na/H exchangers maintain a protonated microenvironment in unstirred layer Fatty acid translocases and fatty acid binding proteins enhance translocation and preferentially bind long-chain fatty acids which do not easily diffuse

Question 31

What happens inside the enterocyte

Answer 31

Re-esterification | Packaging into lipoprotein particles

Question 32

Re-esterification

Answer 32

Smooth Endoplasmic Reticulum (SER) | long chain fatty acids are assembled back into TAGs and phospholipids

Question 33

Packaging into lipoprotein particles

Answer 33

Rough Endoplasmic Reticulum (RER) | Apolipoproteins are synthesized and trafficked to SER and Golgi

Question 34

What happens in the smooth endoplasmic reticulum

Answer 34

Apolipoproteins encounter TAGS, phospholipids and cholesterol esters in SER and form Chylomicrons The largest lipoprotein made primarily of TAGs Surface coated with lecithin and phospholipids Very-low-density lipoproteins (VLDLs) Carry mainly endogenous lipids during both fed and fasting states

Question 35

Trafficking of lipoprotein particles

Answer 35

SER: Vesicles carry chylomicrons and VLDLs to Golgi cis face Golgi Apparatus: Apolipoprotein A-I associates with them here Glycosylation of Apolipoproteins occurs Vesicles carry chylomicrons and VLDLs from Golgi trans face to the basolateral membrane

Question 36

What happens in the lymph

Answer 36

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

Question 37

Water Soluble vitamins

Answer 37

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

Question 38

Fat-soluble vitamins

Answer 38

Called so because of chemical structure and storage in fat deposits Rely on the lipid absorption process because of chemical structure 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

Question 39

What happens with vitamins in the enterocyte

Answer 39

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

Question 40

What happens with vitamins in the lymph

Answer 40

Enter systemic blood | Enter the liver through receptor mediated endocytosis of chylomicrons

Question 41

Fat-soluble vitamin deficiencies

Answer 41

``` Can occur from malabsorption Bariatric surgery drugs that impair hydrolysis drugs that impair bile acids impaired hepatobiliary function unabsorbable fat substrates Treatment: Water-miscible emulsions of the vitamins ```

Question 42

Folate

Answer 42

Deficiency can cause neural tube defects in developing fetus | Spina bifida and anencephaly

Question 43

Tetrahydrafolate

Answer 43

Reduced form of folate Biochemically active form Cofactor Synthesis of thymine and purines

Question 44

Deficiency of tetrahydrafolate results in...

Answer 44

Inhibited DNA synthesis Megaloblastic Anemia Red blood cells in bone marrow become large due to uninhibited protein and RNA synthesis

Question 45

treatment of tetrahydrafolate deficiency

Answer 45

pteroylmonoglutamate (PteGlu1)

Question 46

Digestion of folate

Answer 46

Folate exists in food as folate polyglutamate (PteGlu7) Folate conjugase Removes glutamate residues one by one to PteGlu1 Transported into enterocytes by PteGlu1 Carrier Occurs in small intestine Mechanism of movement through basolateral membrane unknown In liver: enzymatically change it to THF

Question 47

Vitamin B12 (Cobalamin)

Answer 47

Only synthesized by microbes Found in animal products vegetarians at risk Coenzyme transfers a methyl group onto homocysteine to create methionine Methionine an essential aa During deficiency of methionine the body uses intracellular stores of folate Folate and B12 deficiencies cause same megaloblastic anemia

Question 48

Absorption of vitamin b12

Answer 48

Released from protein carriers in stomach via pepsin and low pH Bound by haptocorrin in stomach Intrinsic factor Also secreted in stomach Does not interact with cobalamin until it reaches small intestine HCO-3 secreted by pancreas induces release of cobalamin from haptocorrin cobalamin binds to IF Cobalamin-IF binds receptors on apical surface of enterocytes in ileum Once in the enterocyte Cobalamin and IF dissociate Binds transcobalamin II Required for basolateral exit Delivered through hepatic circulation to liver The liver secretes excess cobalamin into bile The dietary intake is so low the bile and diet cobalamin in small intestine is equal

Question 49

Vitamin B12 Deficiency

Answer 49

Can occur from a vegetarian diet Pernicious anemia 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 Bacteria in small intestine can bind and metabolize it Crohn disease Ileal resection