Digestion and Absorption of Fat

Question 1

Why are fats important?

Answer 1

• calorifically dense, 2x energy compared to carbs and protein, can be stored in an unhydrated form
• fat soluble vitamins: ADEK
• essential fatty acids

Question 2

Give a brief overview of beta-oxidation.

Answer 2

Small amount of ATP required for first step, turns fatty acid into fatty acyl-CoA
FADH2 liberated –> ATP (oxidative phosphorylation)
NADH liberated –> ATP (oxidation phosphorylation)
Acetyl CoA liberated –> Krebs cycle –> ATP
Cycle repeats, the longer the chain the greater the number of times it can go round the cycle and the more energy can be liberated.
Last time it goes through the cycle, 2 x acetylCoA’s are liberated

Question 3

What are the fat soluble vitamins and what are the required for?

Answer 3

A = retinoic acid, vision
D = calcium absorption
E = antioxidant, role in protecting against cancer and CVS, deficiency characterised by poor nerve conduction --> neurological problems 
K = clotting factor, bone metabolism

Question 4

What are the essential fatty acids?

Why are they important?

Answer 4

linoleic acid
linolenic acid
arachadonic acid –> prostaglandins
Formation of healthy cell membranes
Development and functioning of the brain and NS
Production of eicosanoids e.g. PGs
Responsible for regulating BP, viscosity, vasoconstriction, immune and inflammatory responses

Question 5

Of the consumed dietary fat, more than 90% is ……………. What is their structure?
The remainder is…….

Answer 5

90% triglycerides = 3 fatty acid chains esterified onto glycerol
5% phospholipids e.g. sphingolipid - serine rather than glycerol backbone
-5% = cholesterol and lipovitamins

Question 6

Not all fats in the lumber are derived from the diet. Give 4 examples of endogenous lipids in the GI lumen?
Where do they predominately come from?

Answer 6

from bile mostly

1. phospolipids
2. unesterified cholesterol
3. membrane lipids from desquamated cells
4. lipids derived from dead colonic bacteria

Question 7

Emulsification takes place by:
1. 
2.
3.
4.

Answer 7

1. food preparation
2. chewing and gastric churning which allows mixing lingual and gastric juices
3. squirting of gastric contents into the duodenum
4. intestinal peristalsis mixes luminal contents with pancreatic and biliary secretions

Question 8

Fat droplets have a hydrophobic core made up of trigylcerides, and a hydrophilic outer layer made up of phospholipids. What does this prevent?

Answer 8

This prevents coalescing of lipid droplets

Question 9

Describe the role of lingual and gastric lipase lipid digestion

Answer 9

lipid digestion begins in the mouth, lingual lipase –> mostly sensory function
in stomach, both lingual and gastric lipase digest large amounts of lipid
They release a single fatty acid from triglycerides, leaving behind intact diglycerides,

Question 10

Which cells release gastric lipase? What is the stimulus?

Answer 10

chief cells in the stomach in response to gastrin/ACh

Question 11

How and where are the fatty acids chains released by lingual and gastric lipase absorbed?

Answer 11

Long chain fatty acids can’t be absorbed in the stomach as they are insoluble at acidic pH –> remain in the core of triglyceride droplets.
Medium and short chain are ionised at gastric pH, remain in solution and are passively absorbed across the gastric mucosa

Question 12

What happens in patients with pancreatic insufficiency (e.g. CF) that helps to prevent fat malabsorption?

Answer 12

reduced bicarbonate release from the pancreas
chyme remains acidic
prolonged activity of lingual and gastric lipases in the duodenum

Question 13

What happens when the fatty acids generated in stomach reach the duodenum?

Answer 13

They trigger the release of CCK from I cells in the duodenal mucosa.

• stimulates contraction of gall bladder, bicarb rich so helps to neutralise acidic chyme –> optimum pH from pancreatic enzymes
• stimulated secretion of pancreatic enzymes, including lipases and esterases

Question 14

What is the major lipolytic enzyme?
What does it do?
What 4 things does it require for full activity?

Answer 14

pancreatic lipase
hydrolyses all dietary triglycerides not hydrolysed in the stomach
Requires
1. colipase (essential for ligand binding conformation)
2. alkaline pH
3. bile salts
4. fatty acids

Question 15

Like many other pancreatic lipases co-lipase is secreted as a ……………….. (…………….). This is converted its active from by ………..

Answer 15

proenzyme
pro-colipase
trypsin

Question 16

What does pancreatic lipase do?

Answer 16

hydrolyses triglycerides and diglycerides into fatty acids and 2-monoacylgylceride

Question 17

What other pancreatic enzymes hydrolyse lipid enzymes?

Answer 17

phospholipase A2
bacterial lipases
carboxyl ester hydrolase

Question 18

Describe the mechanics of lipid absorption.

Answer 18

Lipid droplets, core of triglycerids and several outer bilayers made up of biles salts, monoglycerids, choleterol,, fatty acid soaps.
PAncreatic lipases hydrolyses triglycerides, as the pool diminshed. the surface lipid layers start to pinch off to forma multilamellar vesicle.
Addition of bile salts –> unilamellar vesicles –> mixed micelles

Question 19

What are the 3 barriers to overcome to absorb the lipolytic products?

Answer 19

1. the mucous gel later that lines the intestinal epithelial surface
2. the unstirred water layer
3. the apical membrane

Question 20

Short/medium chains can easily diffuse through the unstirred water layer and diffuse into the enterocyte.
Describe how long chain fatty acids enter the enterocyte.

Answer 20

Long chain fatty acids held within micelles.
When these reach the enterocyte surface they encounter low pH produced by Na-H exchange and the brush border membrane.
The fatty acids are pronated and leave the mixed micelle to enter the enterocyte by:
- non-ionic diffusion
- collision and incorporation in the cell membrane
- novel evidence of active carrier mediated processes

Question 21

What happens to the bile acids that remain form the micelles?
What happens in disease?

Answer 21

They are recycled at the level of the terminal ileum, where they are redirected to the liver in the portal blood
If you have terminal ileal disease you diminish your store of bile acids, reduce emulsification of fatty acids. Can cause cholesterol stones as cholesterol precipitates out of the micelles

Question 22

Describe what happens to long-chain fatty acids once inside the enterocyte?

Answer 22

bind to fatty-acid binding proteins. This is essential for:
- preventing leaking back out of the enterocyte
- prevents lipid toxicity
- ensuring transfer of fatty acids to the SER
Re-esterified in the SER, absorbed onto apoproteins and termed chylomicrons.
Chylomicrons are trafficked out of the cell and go into the lymph

Question 23

What are the 2 pathways for the different types of fats that need to resesterified in the enterocyte?

Answer 23

Those with a preexsisting backbone –> monoglyceride pathway to add fatty acids
Those without a backbone (e.g. free fatty acids) –> phophatidic acid pathway where are glycerol backbone is made

Question 24

Describe what happens to the exported chylomicrons?

Answer 24

Travel in the lumph.
Come into contact with endothelial surface where they encounter lipoprotein lipase, which hydrolyses triglycerides in the chylomicrons to fatty acids and glycerol, leaving behind remnant chylomicrons.
Fatty acids and glycerol –> muscle and adipose tissue
Remnant –> liver

Question 25

What is fat malabsorption characterised by?

What are the possible causes?

Answer 25

steatorrhea
pancreas insufficiency
terminal ileal disease
lymph disease
pH change in the intestines

Question 26

What is the one licensed drug treatment for obesity?

What does it do?

Answer 26

Orlistat
Inhibits some of the pancreatic lipase
Fat is excreted in stool