Lipid Digestion, Absorption, & Transport

Question 1

3 Major Purposes of Lipid Metabolism

Answer 1

1. Structure = as biological membranes
2. Storage = of chemical energy as burnable fat
3. Signals = between tissues & neighboring cells; (hormones) chemical signals

Question 2

Triacylglycerols are broken down by ____________ ,

and the products are absorbed by the ____________.

Answer 2

Triacylglycerols are broken down by the lipases ,
and the products are absorbed by the intestine .

Question 3

Basic Structure of a triacylglycerol

Answer 3

Triacylglycerols = 90% of lipids ingested by humans & are the major form of energy storage in humans

triacylglycerols consist of glycerol triesters of fatty acids such as palmitic acid and oleic acids.

Question 4

Facts about Lipids ingestested by humans

Answer 4

• 90% of lipids ingested by humans consists of triacylglycerols
• triacylglycerols are the major form of energy storage in humans
• cholesterol, cholesterol esters, phosopholipids, & free fatty acids make up the remaining 10% of lipids ingested by humans

Question 5

Key Ideas Underlying Lipid Metabolism

Answer 5

• Lipids are hydrophobic
• Different aspects of lipid metabolism must accomodate the hydrophobicity
  
  • Digestion-in the small intestine
  • Absorption-into the intestinal cells
  • Transport-throughout the body

Question 6

Digestion of triacylglycerols

Answer 6

Triacylglycerols are digested first before they are absorbed…

• mainly occurs in the small intestine
• take place at the lipid-water interface
  
  • triacylglycerols are water-soluble
  • digestive enzymes are water insoluble
• Factors that assist mixingg of the water & lipid layers
  
  • churning perstaltic movements of the intestine
  • emulsifying action of bile acids

Question 7

What does the rate of triacylglycerol digestion depend on? And what helps increase this?

Answer 7

The rate of triacylglycerol digestion depends on the surface area of the interface, which is greatly increased by the…

churning peristaltic movements of the intestine combined with the emulsifying action of the bile acids

Question 8

____________ act as the lipid-water interface

Answer 8

Lipases act as the lipid-water interface

Question 9

Define…

Lipase(s)

Answer 9

Lipase is the pancreatic enzyme that breaks down dietary fats (triacylglycerols) in the small intestine

• catalyzes the sequential hydrolysis at the 3 and 1 positions
• hydrolyze lipids at the lipid-water interface

Structure of Lipase:

• 449 residues
• N-terminal domain contains the active site and is structurally similar to serine proteases
• C-terminal domain binds colipase

Structural changes on binding micelles:

• 26-residue helical “lid” over the active site opens
• 10 residue β5-loop moves, resulting in generation of the oxyanion hole (positively + charged) that stabilizes negative charge
• hydrophobic surface generated at the active site mouth

Question 10

(Lipase) Interfacial Activation

Answer 10

Lipases hydrolyze lipids at the lipid-water interface…

Enzymatic activity increases at the lipid-water interface

Requires 2 things to bind to the interface:

1. mixed micelles of lipid (PC or triacylglycerols) & bile acids
   
   • ester bonds are oriented toward the surface of the micelle, making them accessible
2. Formation of a 1:1 complex with the 90 residue protein colipase

Question 11

Role of Colipase Binding

Answer 11

1. Colipase’s hydrophobic end extends toward the micelle, helping it bind
2. Colipase forms H-bonds to the open “lid”

Question 13

Define…

Bile Acids

Answer 13

The bile acids (also called bile salts) are….

• amphipathic (detergent-like) molecules that act to solubilize fat globules by dispersing them into micelles. ​
  
  • Emulsifier - act by solubilizing triacylglycerols into micelles (hydrophobic end toward lipid, hydrophobic end toward water)
• cholesterol derivatives
  
  • ​that are synthesized by the liver and secreted as glycine or taurine conjugates into the gallbladder for storage
    
    • ​(stored in the gallbladder).
  • From there they are secreted into the small intestine, where lipid digestion and absorption mainly take place
    
    • ​ (used in the small intestine)

Question 14

Basic features of Lipid Absorption

Answer 14

• occurs at the small intestinal mucosa (cells lining the small intestine)
• What is absorbed?
  
  • smaller bile acid micelles containing…
    
    • fatty acids
    • monacylglycerols
    • diacylglycerols

Question 15

Explain the purpose of bile acids in the absorption of lipids

Answer 15

The Bile Acid Micelles facillitate transport across the unstirred aqueous boundary layer at the intestinal cell wall.

Question 16

Explain the purpose of Fatty Acid Binding Protein (FABP) in the absorption of lipids

Answer 16

Inside the intestinal cells, Intestinal Fatty Acid Binding Protein

(I-FABP) binds and solubilizes lipids in the cytoplasm.

Question 17

___________ transport lipids between the intestines, liver, and other tissues.

Answer 17

Lipoproteins transport lipids between the intestines, liver, and other tissues.

Question 18

Define…

Lipoprotein

Answer 18

Lipoproteins transport lipids between the intestines, liver, and other tissues

Lipoproteins are…complexes of lipid and protein…

• Globular, micelle-like complex of lipids and proteins
• nonpolar core of triacylglycerols & cholesteryl esters
• amphiphillic coating of protein, phospholipid, and cholesterol.

image of low density lipoprotein (LDL)

Question 19

5 Classes of Lipoproteins

(which vary in composition and function)

Answer 19

5 Classes of Lipoproteins

1. Chylomicrons
2. VLDL
3. IDL
4. LDL
5. HDL

Question 20

Lipoprotein Densities

Answer 20

Lipoprotein densities…

Decrease as particle size increases

(this is because the coating is more dense than the interior)

Remember…typical features of a lipoprotein

Exterior: protein, phospholipid, & cholesterol form a ca. 20Å monolayer on the surface

Interior: Triacylglycerols and cholesteryl esters

• Therefore a Lipoprotein with greater % of protein (proportion) will be more dense.*
• &*
• Smaller Diameter → Larger Density*

Question 21

Apolipoproteins (apoproteins)

Answer 21

Apolipoproteins (apoproteins) = The protein components of lipoproteins

There are at least 9 different ones

Typical Features:

• Water-soluble & associate, weakly with lipoproteins
• High helix content (i.e. mostly a-helical proteins)
• Amphipathic helices –
  
  • polar side towards water, phospholipid head
  • nonpolar side toward lipoprotein interior
  • float on phospholipid surfaces like logs on water”

Question 22

Apolipoprotein B-100 (apoB-100) of LDL

Answer 22

Question 23

Apolipoprotein A-1

Answer 23

Question 24

Chylomicrons in Lipid Transport

Answer 24

Chylomicrons (1 of the classes of lipoproteins) are lipoprotein particles that transport dietary triacylglycerols to muscle and adipose tissue, and dietary chloesterol to the liver

Intestinal mucosa: Fatty acids are converted (back) into triacylglycerols. Triacylglycerols & cholesterol are packaged into chylomicrons.

Transport continues through the lymphatic vessels and into the bloodstream.

• Triacylglycerols in chylomicrons are released through hydrolysis by lipoprotein lipases.
• Lipoprotein lipases are located on the inner surface of the capillaries in skeletal muscle and adipose tissues that use fatty acids as fuels or in the synthesis of lipids.
• What remains?
  • The liver takes up the chylomicron remnants, delipidated chylomicrons that are enriched in cholesterol.

Question 25

The **Liver** in Lipid Transport

Answer 25

_The Liver in Lipid Transport...._ * Takes up the chylomicron remnants * Synthesizes * Very-Low density Lipoproteins (VLDL) * Intermediate-density Lipoproteins (IDL) * Low-density Lipoproteins (LDL) Also the major site of endogenous triacylglycerol and cholesterol synthesis. VLDLs, IDLs and LDLs transport endogenous triacylglycerols and cholesterol from the liver to tissue

Question 26

**VLDL**s in Lipid Transport

Answer 26

- VLDLs transport endogenous triacylglycerols and cholesterol from the liver to tissues. - Triacylglycerols in VLDL’s are also degraded by ***lipoprotein lipase*** in the capillaries of skeletal muscle and adipose cells. _Fate of released fatty acids:_ Skeletal muscle * released fatty acids are stored or broken down for energy Adipose tissue * fatty acids are mostly built into triacylglycerols for storage * mobilized in times of need by hormone-sensitive lipase * free fatty acids bind to albumin and are transported in the blood to sites of need Fate of released glycerol backbone: * Converted to dihydroxyacetone phosphate (DHAP, the glycolytic intermediate) in the liver

Question 27

**LDL**s in Lipid Transport

Answer 27

_LDLs in Lipid Transport_ * **LDLs function to deliver cholesterol to tissues** * LDLs are taken up by cells using **Receptor-Mediated Endocytosis**

Question 28

Receptor-Mediated Endocytosis (LDL in lipid transport)

Answer 28

**LDL-receptors** (shown in red) * Cell surface glycoproteins that bind Apolipoprotein B-100 Clustered in clathrin-coated pits **LDL is taken into cells in clathrin-coated vesicles.** * Clathrin is a protein that forms triskelions * Triskelions assemble to form polyhedral cages * The hexagonal barrel is only ~700 Å in diameter, whereas clathrin-coated membranous vesicles are typically ~1200 Å in diameter. **The clathrin coat is stripped and the LDL vesicles fuse with endosomes whose internal pH is ~5.0.** * This pH results in receptor release. * The receptors are recycled back to the cell surface. **The endosomes fuse with lysosomes, vesicles which carry degradative enzymes**. * ApoB-100 is degraded to AAs * Cholesteryl esters are degraded to cholesterol & fatty acids ***Note: Receptor-mediated endocytosis is a general method for the specific intake of large molecules.***

Question 29

Cholesterol Disposal

Answer 29

**_Cholesterol Disposal_** **Only occurs in the Liver** * **Cholesterol is converted to bile acids** * **LDL particles are taken in by receptor-mediated endocytosis** * **HDL particles bind to a Scavenger Receptor class B type I receptor (SR-BI receptor)** * lipids are transferred into the liver without taking in the HDL * HDL dissociates and re-enters the circulation

Question 30

**HDL** in Lipid Transport

Answer 30

**HDLs main function is to transport cholesterol from tissues to the liver** * Function essentially the opposite of LDL * Assembled in the plasma from components of degraded lipoproteins * **Extracts cholesterol from cell-surface membranes** **Lecithin-cholesterol acyltransferase (LCAT)** * HDL-associated enzyme that converts cholesterol to cholesteryl esters * Activated by apoA-I