Digestion and Absorption of Fat Flashcards
What properties of lipids make them the most suitable storage of energy?
They are non polar and can be stored in an anhydrous state.
Why does the ‘apple shape’ distribution of fat pose a higher risk of weight-related health problems?
There is more visceral fat and less subcutaneous fat with the apple shape than with the pear shape.
What are the RQ values for carbohydrates, lipids and proteins?
Carbohydrates: 1
Proteins: 0.8
Lipids: 0.7
What are the 4 steps of b-oxidation?
What is the starting molecule for the cycle?
1 - Oxidation.
2 - Hydration.
3 - Oxidation.
4 - Cleavage.
Starting molecule is fatty acyl-CoA.
What is the function of acyl-CoA synthetase?
To convert fatty acids into fatty acyl-CoA.
Summarise The ATP production of beta oxidation.
- 1 ATP required for initial step.
- Step 1: FAD -> E.T.C produces 2 ATP.
- Step 4: NAD+ -> E.T.C produces 3 ATP.
What is the primary product of beta oxidation?
Acetyl CoA.
How many carbons are removed form the fatty acid chain per turn of the b-oxidation cycle?
2.
Which vitamins are fat soluble?
A, D, E and K.
List 6 symptoms of vitamin A deficiency.
1 - Night blindness.
2 - Corneal drying (xerosis).
3 - Corneal degeneration and blindness (xerophthalmia).
4 - Impaired immunity.
5 - Hypokeratosis.
6 - Keratosis pilaris (bumps on the skin).
List 9 symptoms of a vitamin A overdose.
1 - Hair loss.
2 - Nausea.
3 - Jaundice.
4 - Irritability.
5 - Vomiting.
6 - Blurred vision.
7 - Headaches.
8 - Muscle pain.
9 - Abdominal pain.
Where can vitamin D3 be synthesised?
What can result in vitamin D deficiency?
In the skin.
Inadequate sunlight exposure + inadequate dietary intake can lead to vitamin D deficiency.
List 2 dietary sources of vitamin D3.
Egg yolk and fish oil.
What is vitamin E otherwise known as?
What is its function?
Tocopherol.
Acts as an antioxidant. Has a role in protection against cardiovascular disease and cancer.
List 3 sources of vitamin E.
1 - Vegetable oils.
2 - Corn.
3 - Soybean.
What are the signs of vitamin E deficiency?
Neurological problems (due to poor nerve conduction).
Where can vitamin K be obtained from other than dietary sources?
Vitamin K is produced by intestinal bacteria.
What is the function of vitamin K?
Involved in the carboxylation of glutamate side chains in proteins to form gamma carboxyglutamate residues.
What are the 3 functions of gamma carboxyglutamate residues?
Usually involved in binding calcium.
Involved in the regulation of:
1 - Blood coagulation.
2 - Bone metabolism.
3 - Vascular biology.
Considering the functions of gamma carboxyglutamate, list 3 symptoms of vitamin K deficiency.
1 - Risk of uncontrolled internal bleeding.
2 - Cartilage calcification.
3 - Malformation of developing bone.
List 7 functions of fatty acids such as:
- Linoleic acid.
- Linolenic acid.
- Arachidonic acid.
Where must these fatty acids come from?
1 - Formation of healthy membranes.
2 - Development and function of the nervous system.
3 - Production of eicosanoids, e.g. PGs.
4 - Regulation of blood pressure.
5 - Regulation of blood viscosity.
6 - Regulation of vasoconstriction.
7 - Regulation of immune and inflammatory responses.
- Must come from diet as cannot be derived endogenously.
What makes up > 90% of dietary fat?
Triglycerides.
How do sphingolipids differ from other membrane phospholipids?
They have a serine rather than a glycerol backbone.
List 4 lipids that are found in bile.
1 - Phospholipids (mostly phasphatidylcholine).
2 - Unesterified cholesterol.
3 - Membrane lipids from desquamated cells.
4 - Lipids derived from dead colonic bacteria.
What is phosphatidylcholine?
A phospholipid head group.
Where in the intestine does lipid hydrolysis occur?
In the aqueous environment of the intestinal lumen.
List 4 processes that emulsify lipids (from dietary sources).
What is the purpose of emulsification?
1 - Food preparation (i.e. blending, cooking).
2 - Chewing and gastric churning.
3 - Squirting of gastric contents into the duodenum.
4 - Intestinal peristalsis.
- Emulsification increases SA : Vol ratio and reduces lipid droplet size.
What prevents the lipid particles from coalescing?
- Coating the droplets with membrane lipids, denatured protein, dietary polysaccharides, products of digestion and biliary phospholipids and cholesterol.
- The polar groups project into the water, preventing coalescence of the micelles.
What is the core of lipid micelles composed of?
Triglyceride, which also contains cholesteryl esters and other non-polar lipids.
How do lingual and gastric lipases modify triglycerides?
They release a single fatty acid, leaving behind in tact diglycerides.
Why are the single fatty acids released by lipases not absorbed in the stomach?
They are insoluble at acidic pH, so remain in the core of the triglyceride droplets.
What happens to medium and short chain fatty acids at gastric pH?
They are:
- Ionised,
- Remain in solution,
- Passively absorbed across the gastric mucosa into portal blood.
What proportion of fat digestion occurs in the stomach?
~15%.
How do patients with pancreatic insufficiency compensate for fat malabsorption?
Give an example of a disease that may cause fat malabsorption.
- Lingual and gastric lipase activity is extended in the duodenal lumen (lingual lipase has a low pH optimum).
- Cystic fibrosis is an example of a disease that may cause pancreatic insufficiency.
- CF Also causes a low pH in the duodenum.
What is triggered in the duodenum when fatty acids are present?
The release of CCK from I cells in the duodenal mucosa.
What two processes does CCK stimulate?
1 - The flow of bile into the duodenum by contraction and relaxation of the sphincter of Oddi.
2 - Secretion of pancreatic enzymes, including lipases and esterases from acinar cells.
What is the function of the sphincter of Oddi?
Opens to allow bile and pancreatic juice to flow between the liver / pancreas and the duodenum.
What is the papilla of Vater?
The sphincter of Oddi and its surrounding mucosa protruding into the duodenum.
What is the strongest lipolytic enzyme?
Pancreatic lipase.
Which 4 conditions must be met for full lipolytic activity of pancreatic lipase?
1 - Colipase (essential for ligand binding conformation).
2 - Alkaline pH.
3 - Bile salts.
4 - Fatty acids.
What is colipase secreted as?
pro-colipase
What are the 2 roles of colipase?
1 - Acts as an anchor for the binding of the lipase.
2 - Forms a colipase-lipase complex that can bind to the lipid interface.
What are the products of pancreatic lipase acting on lipids?
Fatty acids
and
2-monoacylglyceride.
What other pancreatic enzymes (other than lipase) hydrolyse lipid esters?
1 - Carboxyl ester hydrolase. AKA cholesterol esterase.
2 - Phospholipase A2.
What does carboxyl ester hydrolase target?
A wide range of esters (low specificity).
What does phospholipase A2 target?
What are the breakdown products?
Glycerophospholipids and their phosphatidylcholine head groups.
Releases a single fatty acid to yield lysophosphatidylcholine.
Which bond does PLA2 target?
Under which conditions is it active and most effective?
Sn-2 acyl bonds of phospholipids.
Most effective at alkaline pH and required bile salts for activity.
Why are in tact triglycerides rarely found in the stools?
Due to the presence of bacterial lipases, which are far more amenable than other lipases.
How do lipolytic products contribute to the mechanisms of lipid breakdown?
By acting as additional emulsifiers to the emulsion droplets.
How does the emulsion droplet change over the course of its breakdown?
Emulsion droplet -> multilamellar vesicle -> unilamellar vesicle -> mixed micelle (composed of bile salts and mixed lipids).
What thins out multilamellar vesicles into unilamellar vesicles?
Addition of bile salts.
Which 3 barriers must lipolytic products overcome to enter enterocytes?
1 - The mucous layer that lines the intestinal epithelial surface.
2 - The unstirred water layer.
3 - The apical membrane of the enterocyte.
How does water solubility change with fatty acid chain length?
What implications does this have on absorption of lipolytic products?
Inversely proportional.
Shorter fatty acids will be able to diffuse through the unstirred water layer more easily, so are absorbed more readily.
Why are fatty acids protonated at the enterocyte surface?
Due to the low pH created by the Na-H exchange at the brush border.
List 3 ways by which fatty acids can enter the enterocyte.
1 - Diffusion.
2 - Incorporation into the cell membrane.
3 - Novel evidence that there is an active carrier mediated process.
After entry of lipolytic products into the enterocyte, where are the remaining bile salts absorbed?
Where are the bile salts redirected to? What is this circulation of bile salts called?
At the terminal ileum and colon.
They are redirected to the liver in the portal blood AKA enterohepatic circulation.
Once in the enterocyte, which molecules are immediately converted back to triglycerides, phospholipids and esters of cholesterol in the SER?
1 - Long chain fatty acids,
2 - Monoglycerides,
3 - Phospholipids,
4 - Cholesterol.
What is an apoprotein?
The protein portion of a complex consisting of a protein molecule joined to a nonprotein protein molecule such as a lipid -> lipoprotein.
Where in the enterocyte do fat droplets form?
In the SER.
Where are apoproteins synthesised?
In the RER.
Where are apoproteins transferred to after being synthesised?
Why are they transferred there?
Transferred from the RER to the SER.
To become associated with lipid droplets to form lipoproteins.
Which molecules pass through the enterocytes’ basolateral membranes to enter capillaries directly from the apical membrane (without re-esterification)?
Glycerol, short and medium chain fatty acids.
Give 2 examples of products of association of apoproteins (from the RER) with lipid droplets (at the SER).
Nascent chylomicrons and VLDLs (very low density lipoproteins).
Where are nascent chylomicrons and VLDLs glycosylated?
At (the cis face of) the golgi apparatus.
*Golgi apparatus: cis face -> golgi stack -> trans face.
What happens to nascent chylomicrons and VLDLs after they are glycosylated?
They are transported in transport vesicles to the basolateral membrane.
They then fuse with the basolateral membrane and are released into lymphatic capillaries.
What is the fate of a long chain fatty acid that enters an enterocyte?
It is re-esterified in the SER in conjunction with apoproteins.
It is then glycosylated at the golgi apparatus and released into lymphatic capillaries as a chylomicron or as a VLDL.
Give 2 examples of substrates that can be used to re-esterify long chain fatty acids to form triglycerides in the SER.
Describe the pathway taken by one of these substrates to form a triglyceride.
1 - Glycerol-3-phosphate.
2 - 2-MG:
- 2-Monoglyceride (2-MG) accepts a FA chain from FA-CoA.
- This produces diacylglycerol and CoA.
- Diacylglycerol accepts another FA chain from another FA-CoA.
- This produces triglyceride and CoA.
What are the 3 reasons for long chain fatty acids binding to fatty acid binding proteins in the enterocyte?
1 - Prevents leakage back out of the enterocyte.
2 - Prevents lipid toxicity.
3 - Ensures transfer of fatty acids to the SER.
Why are glycerol, short and medium chain fatty acids suitable fat substitutes for patients with fat malabsorption?
Because they are transported unmodified directly into blood capillaries through the enterocyte.
What happens to chylomicrons after they are exported from the enterocyte?
- They find their way to the endothelial surface, where they encounter lipoprotein lipase.
- Lipoprotein lipase hydrolyses the triglyceride components of the chylomicrons.
- The products are fatty acids and glycerol, leaving behind remnant chylomicrons.
List 3 lipoproteins, excluding chylomicrons.
1 - VLDLs.
2 - LDLs.
3 - HDLs.
What is the function of HDLs?
HDLs scavenge cholesterol and return it to the liver (protective function).
What is steatorrhoea?
The excretion of abnormal quantities of fat with the faeces owing to reduced absorption of fat by the intestine.
What is Orlistat?
How does it work?
- A medicinal treatment for obesity.
- An inhibitor of lipase.
8 points to summarise this deck:
1 - Importance of fat and b-oxidation.
2 - Fat soluble vitamins.
3 - Essential fatty acids.
4 - Digestion.
5 - Action of emulsification, fat droplet formation, lipase action and bile acids.
6 - Absorption and processing into triglycerides and incorporation in chylomicrons.
7 - Fate of chylomicrons.
8 - Obesity.
