Lipids 2: Lipid Digestion, Absorption and Transport Flashcards
What is the length of most FAs found in food?
Most abundant is the long chain FAs >12 carbons long
* short chain FAs of C2-C4 are not a major component
* medium chain FAs are also not a major component
What is the most common form of ingested FAs?
> 90% is in the form of TG
How much ingested fat in is excreted in feces?
Only 4%
* Highly saturated fat is the expection because it is harder to solubilize
What is a critical biological property for digestion and absorption of fats?
The solid-liquid phase change of fats
What are the three classes of dietary lipids?
- triacylglycerides
- phospholipids
- cholesterol
How are ingested lipids presented for digestion?
Presented as micelles or tiny fat droplets (containing all 3 lipid classes) via bile and then specific enzymes break it down more individually.
What is the major and minor enzymes for TG digestion?
- Pancreatic lipase (major)
- gastric lipase (minor)
- lingual lipase (minor)
What are the following properties for pancreatic lipase?
* dietary lipid it acts on
* preferred environment
* specificity
* site of action
* cofactors
- TGs
- preferred environment: pH 5-6
- specificity: sn-1 and sn-3 positions
- site of action: SI lumen oil and aqueous phase interface
- cofactors: colipase
What are the products of pancreatic lipase?
2-monoglycerols + free fatty acids
What are the following properties for gastric lipase?
* Dietary lipid it acts on
* preferred environment
* specificity
* site of action
- Dietary lipid it acts on: TGs
- preferred environment: acidic medium optimal pH 4
- specificity: medium chain FAs on TG therefore milk fat hydrolyzed efficiently in infacts; FAs at sn-3
- site of action: stomach, jejunum
What is the product after gastric lipase?
1,2-diacylglyceride + free fatty acids
What are the following properties for lingual lipase?
* Dietary lipid it acts on
* preferred environment
* specificity
* site of action
- Dietary lipid it acts on: TGs
- preferred environment: acid stable
- specificity: hydrolyzes at sn-3; milk fats?
- site of action: stomach
What are the following properties for cholesterol esterase?
* Dietary lipid it acts on
* preferred environment
* specificity
* site of action
* cofactors
- Dietary lipid it acts on: cholesterol
- preferred environment: mixed micells
- specificity: non-specific
- site of action: SI
- cofactors: stimulated by bile salts
What are the major locations for digestion and absorption of fats?
- mouth and salivary glands
- stomach
- Small intestine
- Large intestine
Describe digestion and absorption of fats in the mouth
Some hard fats begin to melt as they reach body temperatures. Sublingual salivary gland in the base of the tongue secretes lingual lipase
Describe digestion and absorption of fats in the stomach
~ 15% of fats broken down here, most digestion and absorption occurs in the SI
* Once the fat reaches the stomach, acid-stable lingual lipase initiates lipid digestion by hydrolyzing one bond of TG to produce diglycerides and FAs. More prominent for milk fats
* The stomach churning action mixes fat with water and acid and gastric lipase can access and hydrolyze a small amount of fat
Describe digestion and absorption of fats in the small intestine
The presence of chyme in to SI leads to the release of CCK from the intestinal mucosa.
* CCK stimulates the release of bile acids from the gall bladder via the common bile duct into the SI which emulsifies the fat in order for enzymes to be able to work on them.
* CCK also stimulates the release of pancreatic lipase from the pancreas via pancreatic duct which turns the emulsified fats of TGs into monoglycerides, glycerol and fatty acids which can then be absorbed
Describe digestion and absorption of fats in the large intestine
Some fat and cholesterol trapped in fibre, exit in feces
what enzymes are important in the digestion of TGs for infants?
gastric lipase and ligual lipase because they have very little pancreatic lipase
Describe the emulsification process of lipids
- in the stomach, the fat and watery GI juices tend to separate hence enzymes cant really get at the fat.
- When fat enters the SI, the gallbladder secretes bile which has an affinity for both fat and water so can bring fat into the water
- Biles emulsifying action converts large fat globules into small droplets that repel each other
- After emulsification more fat is now exposed to the enzymes making fat digestion more efficient
What is the role of the cofactor colipase?
Colipase is a cofactor for pancreatic lipase which binds to both bile salts as well as lipase, thus assisting the enzyme in breaking down TGs
How does pancreatic lipase break down TGs?
- the TG (sn-1 & sn-3) and two molecules of water are split.
- The H and OH from water complete the structures of two fatty acids and leave a monoglyceride (FA left on sn-2)
What happens to the monoglyceride and FA products after pancreatic lipase?
These products (FAs, monoglycerides, glycerol) may pass into the intestinal cells
* sometimes the monoglyceride is split with another molecules of water to give a third FA and glycerol
Summary of major events and secretions of TG digestion and absorption
What is orlistat?
Drug that inactivates gastric and pancreatic enzyme so effects the stomach and SI.
* Blocks these enzymes by preventing fatty acid absorption and are excreted.
What is the major and minor enzyme of phospholipid digestion?
- pancreatic phospholipase A2 (major)
- pancreatic phospholipase B (minor)
What are the following properties for phosopholipase A2?
* Dietary lipid it acts on
* preferred environment
* specificity
* site of action
- Dietary lipid it acts on: phospholipids, mostly phosphatidylcholine
- preferred environment: mixed micelles
- specificity: FAs at sn-2 position
- site of action: SI
What are the following properties for phospholipase B?
* Dietary lipid it acts on
* preferred environment
* specificity
* site of action
- Dietary lipid it acts on: phospholipids
- preferred environment: ?
- specificity: ?
- site of action: intestinal mucosa
What is the major phosphlipid that is digested?
phosphotidylcholine
What are the products of phosphatidylcholine after phospholipase A2?
lysophosphatidylcholine + free fatty acid
What is the form of most dietary cholesterol?
- mostly free cholesterol which can be absorbed
- 10-15% is presented as an ester, but cannot be absorbed in this form so has to be broken for by enzyme first
What is the major enzyme of cholesterol digestion?
pancreatic cholesterole esterase secreted as an active enzyme which hydrolyzes
* FAs on the cholesterol esters
* FAs at all positions on TG, PL, esters of fat soluble vitamins
non-specific esterase
What is the storage form of cholesterol?
cholesterol esters
How do lipids cross the unstirred water layer to be absorbed by the enterocyte?
- free fatty acids can pass right through to be absorbed
- mixed micelles are more soluble in the unstirred warer layer and can easily cross the unstirred water and once in contact it can transport content through the cell via different transport mechanisms
What is contained in mixed micelles?
- bile salts
- lipids: MAG, fatty acids, lysophosphatidylcholine, cholesterol
How are lipids taken up into the entercyte?
- passive diffusion
- carrier mediated transporters on BBM
What lipids are absorbed via passive diffusion?
- glycerol, SCFA, MCFA
- micelle delivery: LCFA, MAGs, cholesterol, lysophosphatidylcholine
What happens in micelle delivery for lipid absorption?
passive diffusion whereby the micelle comes in contact with the membrane and delivers its contents straight into the cells
What lipids are absorbed via carrier mediated transporters?
- FAs via fatty acid binding protein (FABP)
- Sterols via Niemann Pick C1 like 1 protein NPC1L1
How does NPC1L1 work?
major sterol transporter
* micelle comes in contact with the transporter on the membrane and allows for the sterols to move in then an endosome separates the different sterols such that cholesterols move forward with absorption and plant sterols are sent back out.
What are phytosterols?
steroid compounds similar to cholesterol which occur in plants
* richest naturally occuring are in vegetable oils and nuts
* approved by Health Canada to be added to mayonnaise, spreads, etc.
What claim has Health Canada approved in regards to phytosterols?
Plant sterols help reduce [or help lower] cholesterol
How do phytosterols lower cholesterol?
through a competition aspect
* The cell structure of phytosterols looks and acts like cholesterol, so it competes with cholesterol for absorption by your digestive system. When your body digests plant sterols instead of cholesterol, it removes some of the cholesterol as waste. This results in lower cholesterol levels and improved health.
Describe the absorption of phytosterols
The are absorbed with cholesterol from the micelle via the NPC1L1 transporter and then an endosome sorts the sterols and plant sterols are pumped back out via ATP-binding cassette sub-family G member 5/8 (ABCG5/8) transporters to be excreted into the feces
Describe the mechanisms of action of phytosterols
- presence in intestinal lumen inhibits intestinal absorption of cholesterol
- reduce amount of cholesterol in micelles
What is ezetimbe?
treatment for CVD
* A drug that blocks NPC1L1 and prevents cholesterol from getting into the cell.
What is enterhepatic circulation of bile acids?
Essentially the recycling of bile acids whereby 90% is reabsorbed.
What is cholestyramine?
A bile acid sequestrant/ bile acid binding drug which prevents bile acid from being reabsorbed thus lowering high cholesterol levels in the blood and remove bile acids via excretion
How are lipids metabolized once absorbed into the enterocyte?
In the enterocyte. lipids are re-esterified/ re-formed into TGs, cholesterol esters and phosphlipids
What are the 2 pathways to reform TGs?
- monoacylglycerol pathway
- glycerol 2-phosphate pathway
What is the monoacylglycerol pathway?
Major reformation of TGs in the enterocyte using enzymes found on the ER.
* monoacylglycerol transferase (MGAT) adds an acyl group to the monoacylgycerol to form a diacylglycerol
* diacylglycerol transferase (DGAT) addis a secondary acyl group to diacyglycerol to form TG
* Once TG is formed it is packaged into chylomicron before leaving cell
What is the glycerol 3-phosphate pathway?
- A pathway to reform TGs in the enterocytes when the monoacylglycerol pathway is lacking
- OR, to form phosphlipids
How does the glycerol 3-phosphate pathway form TGs?
- glycerol phosphatase acyltransferase (GPAT) adds 2 acyl groups to the glycerol 3-phosphate
- phosphatidate phosphatase removes the phosphate group forming a diacylglycerol
- diacylglycerol acyltransferase (DGAT) adds another acyl group to the diacylglycerol forming TG
How does the glycerol 3-phosphate pathway form PLs?
- glycerol phosphatase acyltransferase (GPAT) adds 2 acyl groups to the glycerol 3-phosphate
How are cholesterol ester reformed in enterocytes?
Cholesterol binds to Acyl-CoA via enzyme Aceyl-CoA cholesterol acyltransferase (ACAT)
How is phosphotidylcholine reformed in enterocytes?
lysophospatidylcholine is reacylated via some sort of acyltransferase enzyme
What is the general transport of non-lipid soluble lipids?
not lipid soluble: TG, cholesterol esters, PL
1. packaged in lipoproteins synthesized in the enterocyte
2. form chylomicrons
3. go into lymph system
4. drain into peripheral circulation at the thoracic dict/ left subclavian vein
5. uptake of CM-remnants by tissues and liver (80-90%)
What is the general transport of lipid soluble lipids?
glycerol, SCFA, MCFA
1. hepatic portal vein
2. liver
