GB 10. Digestion and Absorption of Lipids. The Handling of Iron in the Body Flashcards by Jennita Ariaratnam

What is the structure of a triacylclycerol?

1 glycerol molcules

- 3 fatty acid chains

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What is a saturated fatty acid?

fatty acid with NO double bonds

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What is monounsaturated fatty acids?

fatty acid with 1 double bond

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What is polyunsaturated fatty acids?

fatty acid with 2 or more double bonds

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What are the 3 principle sites of lipid digestion? What is involved in each site?

[1] MOUTH

mastication
emulsification
lingual lipase

[2] STOMACH
- gastric lipase

[3] SMALL INTESTINE

pancreatic enzymes
emulsification

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What is emulsification of lipids in the mouth? What does it allow for?

breakdown of large droplets of lipid into tiny droplets
requred for efficient digestion of lipids
allows enzymes to gain access to lipid substrates
starts with chewing (mastication)

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What enzymes are involved in the breakdown of lipids in the stomach? Describe the enzymes a bit

[1] Lingual Lipase
[2] Gastric Lipase

both are lipases
relatively acid stable
act on TAGs with short to medium FA chains (less than 12 carbons)
important in neonates (to digest milk fat) and patients lacking pancreatic lipase [!!!]

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Emulsification first occurs in the mouth, but is then further continued in…

the intestine

- specifically, the duodenum

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What happens during emulsification in the intestine?

it increases the surface area of lipid droplets so enzymes can work at lipid/aqueous interface

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How is emulsification of lipids in the small intestine achieved by? [2]

[1] Bile Salts - detergent properties

[2] Peristalsis - mechanical mixing

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What are the pancreatic enzymes involved in the digestion of lipids? Explain some processes.

[1] Pancreatic Lipase
- binds to surface of droplet in presence of Pancreatic Colipase

[2] Colipase-Lipase Complex (Pancreatic Lipase)

spreads over surface of droplet
leads to hydrolysis of triglycerides to monoacylglycerol and fatty acids

[3] Cholesterol Esterase

hydrolyzes cholesteryl esters to cholesterol + free fatty acids
activity increased by bile salts

[4] Phospholipase A2

digests phospholipid to lysophospholipid by removing 1 fatty acid
activated by trypsin
requires bile salts for optimum activity

[5] Lysophospholipase

removes remaining fatty acid at C1
leaving glycerylphosphoryl base: excreted, further degraded or absorbed

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The products of fat digestion are formed into what?

Mixed Micelles

bile salts
free fatty acids
free cholesterol
2-monoacylglycerol

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What do mixed micelles contain?

Mixed Micelles

bile salts
free fatty acids
free cholesterol
2-monoacylglycerol

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Explain how lipids are absorbed by enterocytes. [2]

[1] Micelle has Hydrophilic Surface

can cross water layer brush border of enterocyte
transports hydrophobic lipids across border

[2] Short/Medium Chain FAs
- do NOT require mixed micelles for absorption

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After they are absorbed, lipids can be excreted from enterocytes to aid in chylomicron formation. Explain this.

fatty acids and monglyceride are transported into the ER where they are used to make TRIGLYCERIDE
triglycerides are grouped with:
– cholesterol esters
– free cholesterol
– phospholipids
– vitamins
– apolipoprotein B48
they form into chylomicrons
they then go to Golgi Apparatus

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After the formation of chylomicrons, what happens to them?

they are excreted from Golgi Apparatus into EXOCYTOTIC VESICLES
transported to basolateral aspect (membrane) of enterocyte
the vesicles fuse with plasma membrane and undergo exocytosis
chylomicrons enter extracellular space and enter lymph

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What are the primary products of lipid digestion?

[1] Free Fatty Acids
[2] Free Cholesterol
[3] 2-Monoacylglycerol

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What is the secretion of pancreatic enzymes controlled by?

it is hormonally controlled

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The absorption of lipids and fat-soluble vitamins (vitamin A,D,K,E) are dependent on 3 factors which are:

[1] Bile Salts
[2] Normal Pancreatic Function
[3] Normal Intestinal Cells

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What are the causes of some Malabsorption syndromes?

[1] Pancreatic Insufficiency
- chronic pancreatitis

[2] Inadequate Mucosal Surface
- as in coeliac disease (gluten sensitivity) due to flattening of villi

[3] Inflammatory States

Crohn’s Disease
may affect entire bowel

[4] Infection
- acute (salmonella) or chronic (tropical sprue) leading to intestinal hurry

[5] Surgery
- surgical resection or fistulae of small bowel

[6] Cystic Fibrosis
- pancreatic enzyme deficiency

[7] Disaccharidase Deficiency

e.g. congenital or acquired lactase deficiency
or congenital sucrase-isomaltase deficiency

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What are the symptoms of malabsorption? What is it normally accompanied by?

weight loss + weakness
failure to thrive (babies)

frequently accompanied by….

steathorrhoea (visible fat in stools)
intestinal discomfort
diarrohea

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How is malabsorption usually detected?

endoscopy/biopsy
serum enzymes in case of pancreatitis

note: it MUST be treated!

Not everything can be digested and some main examples are…

[1] digestion of most nutrients is incomplete

[2] Keratins + Plant Polymers (such as Cellulose + Pectin) are not digested

[3] some veggies contain Indigestible Carbs

How much iron does the body normally contain?

2 to 4 grams of iron

What is the reduced form of iron?

Fe2+ | - ferrous

What is the oxidized form of iron?

Fe3+ | - ferric

What is the ferrous form?

Fe2+ | - reduced

What is the ferric form?

Fe3+ | - oxidized

A lot of iron in the body goes towards...

- haemoglobin

What are the 3 main categories that iron is used towards in the body?

[1] Haemoglobin [2] Myoglobin + Enzymes [3] Storage Iron

What is the most common micronurient deficiency?

Iron Deficiency

When iron levels drop, what happens?

[1] storage iron is mobilized first | [2] haemoglobin synthesis is impaired

What can iron deficiency result in?

results in microcytic hypochromic anaemia

How do you treat iron deficiency?

iron supplements

What is Haemosiderosis?

- accumulation of ferritin and hemosiderin | - leads to free radical generation

What is Haemochromatosis? What may it be caused by?

- progressive hemosiderosis - results in organ damage - associated with a mutation in HFE gene (human hemochromatosis protein)

How do you treat iron overload?

[1] Repeated Phlebotomy | [2] Iron Chelator: Desferrioxamine

What are the 2 major forms of dietary iron?

[1] Haem Iron | [2] Non-Haem Iron

What is haem iron derived from? How is it absorbed?

- derived primarily from haemoglobin + myoglobin in animal protein sources (red meat) - it must be hydrolyzed from any protein it is attached to first - then absorbed readily but slowly overall absorption from meat is about 20 to 25%

Where does Non-Haem Iron come from?

- bound to some other organic constituent of food (cereals, pasta, beans, dark green leafy veggies) - cooking tends to break these interactions and increase iron availability

What are the 2 changes of oxidation state that iron undergoes during digestion and absorption? Describe the change of state, location and so on.

[1] Fe3+ reduced to Fe2+ - stomach - favoured by low pH (HCl) - reducing agents (like ascorbic acid) assist the process - *reduction important as Fe2+ dissociates from ligans more easily than Fe3+ [2] Fe2+ oxidized to Fe3+ - duodenum (bicarbonate rich and alkaline) - in alkaline environment, haem absorbed directly by mucosal cells - within mucosal cells, iron dissociates from it - free Fe2+ oxidized to Fe3+ and taken up by mucosal cells

How is haem aborbed? What is the transporter involved?

- haem absorbed entirely into the enterocyte - transporter: Haem Carrier Protein 1 - Fe2+ is released from haem by haem oxidase

Which transporter moves haem into the enterocyte?

Haem Carrier Protein 1

How is Non-Haem Iron absorbed into the enterocyte?

- Fe3+ is reduced by the reductase Duodenal Cytochrome B (DcytE) to Fe2+ - Fe2+ transported into enterocyte via Divalent Metal Transporter 1 (DMT1) only!

What are the 2 fates of iron after entering the enterocyte?

[1] stored as cystolic iron as Ferritin [2] transported across the basolateral membrane via Ferroportin (FPN) - Fe2+ converted back to Fe3+ by Hephaestin - Fe3+ binds to Transferrin for transport around body

What happens to iron after it enter the blood circulation?

- Fe2+ converted back to Fe3+ by Hephaestin | - Fe3+ binds to Transferrin for transport around body

Iron absorption is reduced by the presence of...[5]

``` [1] Tannins [2] Oxalate [3] Phytate [4] Inorganic Phosphates [5] Phosphate containing Antacids ```

What is iron deficiency anaemia a result of?

a result of poor iron absorption

What is apotransferrin?

transferrin without a Fe3+

Where does transferrin-bound iron go to?

[1] to iron stores | [2] to bone marrow

How does iron enter a cell? Explain the process.

[1] enters by endocytosis through a Transferrin Receptor [2] a CURL (compartment of uncoupling of receptor and ligand) is formed [3] Fe3+ is released and stored in ferritin in the cytoplasm of cell [4] apotransferrin is recycled to surface of cell

What is a CURL?

Compartment of Uncoupling of Receptor and Ligand

What state is iron mostly stored in? Where and how is it stored?

- mainly sotred in ferric state (Fe3+) - stored as part of complex ferritin - protein forms a shell that contains about 3000 Fe3+ in form of ferric oxide hydroxide (FeOOH) crystals