GB 10. Digestion and Absorption of Lipids. The Handling of Iron in the Body Flashcards
What is the structure of a triacylclycerol?
- 1 glycerol molcules
- 3 fatty acid chains
What is a saturated fatty acid?
fatty acid with NO double bonds
What is monounsaturated fatty acids?
fatty acid with 1 double bond
What is polyunsaturated fatty acids?
fatty acid with 2 or more double bonds
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
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)
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 [!!!]
Emulsification first occurs in the mouth, but is then further continued in…
the intestine
- specifically, the duodenum
What happens during emulsification in the intestine?
- it increases the surface area of lipid droplets so enzymes can work at lipid/aqueous interface
How is emulsification of lipids in the small intestine achieved by? [2]
[1] Bile Salts - detergent properties
[2] Peristalsis - mechanical mixing
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
The products of fat digestion are formed into what?
Mixed Micelles
- bile salts
- free fatty acids
- free cholesterol
- 2-monoacylglycerol
What do mixed micelles contain?
Mixed Micelles
- bile salts
- free fatty acids
- free cholesterol
- 2-monoacylglycerol
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
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
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
What are the primary products of lipid digestion?
[1] Free Fatty Acids
[2] Free Cholesterol
[3] 2-Monoacylglycerol
What is the secretion of pancreatic enzymes controlled by?
it is hormonally controlled
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
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
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
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
