Lipid Digestion, Absorption, & Transport Flashcards
Lipid Metabolism: Chapter 20
3 Major Purposes of Lipid Metabolism
- Structure = as biological membranes
- Storage = of chemical energy as burnable fat
- Signals = between tissues & neighboring cells; (hormones) chemical signals
Triacylglycerols are broken down by ____________ ,
and the products are absorbed by the ____________.
Triacylglycerols are broken down by the lipases ,
and the products are absorbed by the intestine .
Basic Structure of a triacylglycerol
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.
Facts about Lipids ingestested by humans
- 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
Key Ideas Underlying Lipid Metabolism
- 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
Digestion of triacylglycerols
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
What does the rate of triacylglycerol digestion depend on? And what helps increase this?
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
____________ act as the lipid-water interface
Lipases act as the lipid-water interface
Define…
Lipase(s)
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
(Lipase) Interfacial Activation
Lipases hydrolyze lipids at the lipid-water interface…
Enzymatic activity increases at the lipid-water interface
Requires 2 things to bind to the interface:
-
mixed micelles of lipid (PC or triacylglycerols) & bile acids
- ester bonds are oriented toward the surface of the micelle, making them accessible
- Formation of a 1:1 complex with the 90 residue protein colipase
Role of Colipase Binding
- Colipase’s hydrophobic end extends toward the micelle, helping it bind
- Colipase forms H-bonds to the open “lid”
Define…
Bile Acids
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)
-
that are synthesized by the liver and secreted as glycine or taurine conjugates into the gallbladder for storage
Basic features of Lipid Absorption
- occurs at the small intestinal mucosa (cells lining the small intestine)
- What is absorbed?
-
smaller bile acid micelles containing…
- fatty acids
- monacylglycerols
- diacylglycerols
-
smaller bile acid micelles containing…
Explain the purpose of bile acids in the absorption of lipids
The Bile Acid Micelles facillitate transport across the unstirred aqueous boundary layer at the intestinal cell wall.
Define…
Lipoprotein
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)
Apolipoprotein B-100 (apoB-100) of LDL
Apolipoprotein A-1
Chylomicrons in Lipid Transport
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.
The Liver in Lipid Transport
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
VLDLs in Lipid Transport
- 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
LDLs in Lipid Transport
LDLs in Lipid Transport
- LDLs function to deliver cholesterol to tissues
- LDLs are taken up by cells using Receptor-Mediated Endocytosis
Receptor-Mediated Endocytosis
(LDL in lipid transport)
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.
