Lipid digestion, Ca, Fe and vitamin absorption

Question 1

How is fat emulsified so it can be absorbed?

Answer 1

Mouth - chewing
Stomach - gastric churning and squirting through the narrow pylorus - mixing with digestive enzymes from stomach and mouth
Small intestine - segmentation and peristalsis mix the luminal content with pancreatic and biliary secretions

Question 2

What is the benefit of the emulsified fat droplets?

Answer 2

increase the surface area to volume ratio

larger surface for lipases and other esterases to digest

Question 3

What is the structure of a the droplets?

Answer 3

Multilamellar vesicles - a hydrophilic coat with - products of lipid digestion, cholesterol, biliary phospholipids, bile salts (when the droplets have progressively been reduced to unilamellar and mixed micelles)

Question 4

Where do lipases work?

Answer 4

On fat at the water-lipid interface

Question 5

What occurs in the gastric phase of fat absorption?

Answer 5

gastric lipase (and lingual lipase in saliva) 
Hydrolyse the triglycerol to give a diacyl glycerol and free fatty acid 
this phase is particularly important in pancreatic insufficiency

Question 6

What are the properties of gastric lipase?

Answer 6

• has a pH optimum of 4 - resistant to pepsin
• inactive in duodenum due to high pH
• hydrolyses TAGs at the 3 position

Question 7

What occurs in the intestinal phase of fat metabolism?

Answer 7

pancreatic TAG lipase, secreted by acinar cells in response to CCK which also stimulates bile flow, mainly hydolyses TAGs at the 1 & 3 positions.
onverts TAGs to 2-monoacylglycerol and 2 free fatty acids
Additional lipases in the duodenum include carboxyl ester hydrolase and phospholipase A2

Question 8

What is the role of bile salts in fat metabolism?

Answer 8

help emulsify the large lipid droplets to small droplets - increase SA for pancreatic lipase but block the access to the TAGs
- colipase binds to bile salts and lipase allowing access to the TAGs & DAGs

Question 9

What does a failure to release bile salts results in?

Answer 9

lipid malabsorption - steatorrhoea (fat in faeces)

secondary vitamin deficiency due to failure to absorb fat soluble vitamins (A,D, E and K)

Question 10

Where does colipase come from?

Answer 10

an amphipathic polypeptide secreted with lipase from the pancreas
secreted as inactive procolipase which is activated by trypsin

Question 11

How is the size of the lipid droplet decreased to a mixed micelle?

Answer 11

TAGs towards the surface of the emulsion droplets are hydrolysed, they are replaced by TAGs within the core, decreasing droplet size

Question 12

How are free fatty acids and monoacylglycerols absorbed?

Answer 12

passive diffusion and/or membrane fatty-acid translocases, fatty-acid binding protein and fatty-acid transport proteins
short and medium chains diffuse through ans exit at the basolateral membrane entering the villus capillaries
long chains are resynthesized to TAGs in the endoplasmic reticulum and are subsequently incorporated into chylomicrons

Question 13

How is cholesterol absorbed?

Answer 13

transport by endocytosis in clatherin coated pits by Niemann-Pick C1-like 1 (NPC1L1) protein

Question 14

What is the effect of ezetimide (a second line drug for hypercholesterolaemia)?

Answer 14

binds to NPC1L1 preventing internalisation of the cholesterol

Question 15

How is Ca2+ absorbed in the small intestine?

Answer 15

both passive (paracellular - all the way along the small intestine) and active (transcellular - duodenum and upper jejunum) transport mechanisms 
In chyme the absorption is mainly active as there is a very small concentration of Ca

Question 16

What is the significance of iron?

Answer 16

an important constituent of haemoglobin and myoglobin and acts as co-factor for numerous enzyme-mediated processes
crucially important in carriage of oxygen by haemoglobin

Question 17

How is iron lost from the body - an unregulated process?

Answer 17

urine
sweat
blood loss
desquamated enterocytes

Question 18

How is iron balance in the body achieved?

Answer 18

Through tight regulation of iron absorption across the duodenum - matching losses

Question 19

Why is iron balance required?

Answer 19

iron deficiency causes microcytic anaemia
iron excess is toxic due to accumulation in liver, pancreas and heart and molecularly the production of hydroxyl radicals and hydroxide ions

Question 20

How is iron absorbed across the enterocyte?

Answer 20

Fe2+ absorbed across the apical membrane by transport process
Fe2+ conveyed to basolateral membrane via a ‘molecular chaperone’
Fe2+ transported across the basolateral membrane by transport process
Fe2+ oxidized to Fe3+ and then transported to tissues
Import of haem across apical membrane followed by cytoplasmic metabolism to release Fe2+

Question 21

How is vitamin B12 absorbed?

Answer 21

ingested in food bound to proteins
stomach acid releases vit B12 from protein
Haptocorin secreted in saliva binds to vitamin B12 which is released in the stomach
Stomach parietal cells release intrinsic facter
Pancreatic proteases digest haptocorin in the small intestine releasing vitamin B12
Vit B12 then binds to the intrinsic factor and the complex is absorbed in the terminal ilium by endocytosis

Question 22

How are fat soluble vitamins A, D, E & K absorbed?

Answer 22

requires adequate bile secretion ans intact intestinal mucosa
Incorporated into mixed micelles
Usually passively transported into enterocytes
Incorporated into chylomicrons, or VLDLs
Distributed by intestinal lymphatics

Question 23

How are water soluble vitamins B (but not B12) C & H absorbed?

Answer 23

similar to aminoacida, monosaccharides etc
Vit B9 - sodium independent (proton coupled folate transporter)
Vit C - sodium dependent
Vit H - sodium dependent

Question 24

How are chylomicrons formed?

Answer 24

Inside the enterocyte
TAGs are synthesised then the ER adds cholesterol esters and phospholipids forming a nascent chylomicron
Apolipoprotein (ApoB-48) is added and the chylomicron is released

Question 25

How is active Ca absorption regulated?

Answer 25

by 1,25-dihydroxyvitamin D3 and parathyroid hormone increasing 1,25-dihydroxyvitamin D3 synthesis

Question 26

What iron is found in the diet?

Answer 26

mainly oxidised Fe3+ (but inly Fe2+ can be absorbed across the apical membrane of the duodenal enterocytes)

• inorganic iron
• haem
• ferratin

Question 27

What promotes the reduction of Fe3+to Fe2+?

Answer 27

HCl in the stomach
Vitamin C
ferric reductase, duodenal cytochrome B (Dctyb), present on the brush border membrane of enterocytes
gasteroferrin, secreted by gastric parietal cells, reversibly binds Fe2+ preventing the formation of insoluble anion salts