Lipid digestion, absorption and transport

Question 1

Give some facts about lipids?

Answer 1

Lipids are a storage form of metabolic energy
We can store much more fat than glucose
Seeds contain high concentrations of lipids to support early growth and development
Triacylglycerols provides 1g fat = 9 kcal (39 kJ)

We can store an unlimited amount of triacylglycerol in adipose tissue
Adipose tissue protects vital organs, giving our bodies and faces their shape

Question 2

What are the roles of lipids?

Answer 2

• Constituents of membranes: cholesterol, phospholipids, sphingolipids and glycolipids
• Sources of metabolic energy: Triacylglycerols (storage), fatty acids and ketone bodies
• Hormones: steroids and eicosanoids
• Others: bile salts (digestion) and waxes (waterproofing)

Lipid metabolism refers to the processes that involve the creation and degradation of lipids

Question 3

What are some types of lipids?

Answer 3

Fatty acids
Triacylglycerols
Glycerophospholipids
Sterols

Question 4

Describe fatty acids?

Answer 4

May be saturated or unsaturated
Vary in length C4 – C22
Many can be synthesised (in the liver) but some cannot

Essential fatty acids – PUFAs – are precursors for important signalling molecules – prostaglandins thromboxanes
These can’t be synthesised (taken in through diet) - containing many double bonds

Question 5

Describe triacylglycerols?

Answer 5

Made up of glycerol, ester and fatty acids
To form they undergo an esterification reaction: carboxylic acid + alcohol -> carboxylic ester + water
They are the main storage form of lipids in humans
TAG may be solid or liquid depending on fatty acid composition

Question 6

Describe glycerophospholipids?

Answer 6

They are major components of cell membranes
C1 position is usually saturated C16 or C18 fatty acid
C2 position often unsaturated fatty acid C16 – C20
This leads to a difference in structure i.e. A kink in the chain

Question 7

Describe sterols?

Answer 7

All sterol molecules based on 4 fused non-planar rings

e.g. cholesterol

Question 8

What is the pathway of lipids?

Answer 8

Digestion
Absorption
Transportation

Question 9

Give an overview of digestion?

Answer 9

This takes place predominantly in the duodenum and ileum
In the mouth: Lingual lipase (negligible role in humans, important in rats)
Stomach: Gastric lipase- up to 30% of lipid digestion
Pancreas/small intestine: Pancreatic lipases (e.g. triacylglycerol lipase and phospholipase A)

Question 10

Why do lipids have to be digested? How is it overcome?

Answer 10

Lipids are hydrophobic but the enzymes which digest them are hydrophilic/water soluble
In a hydrophilic environment lipids form large droplets – inaccessible to enzymes which act at the lipid-water interface

We need a large surface area given by the churning peristaltic movements of the intestine and bile acids/salts are a large factor

Question 11

Describe bile acids and salts?

Answer 11

They are amphipathic detergent-like molecules and emulsify dietary fats in the duodenum
Produced in the liver from cholesterol
Secreted into the duodenum via the bile duct, as glycine or taurine conjugates
Stored in the gallbladder
Increases surface area available for enzyme action

Question 12

Describe pancreatic lipases?

Answer 12

This hydrolyses triacylglycerols
Ester hydrolysis (saponification) gives a carboxylic acid and an alcohol
Lipase hydrolysis of a triacylglycerol gives a fatty acid (salt form = soap) plus mono- & di-acylglycerols
Fatty acids are essentially removed one at a time by the enzyme

Question 13

How does the enzyme pancreatic lipase work?

Answer 13

Lipase is activated by interaction with lipid-water interface (‘interfacial activation’)
Activity requires mixed micelles of phosphatidylcholine and bile acids, and pancreatic colipase (a 90-residue protein) that forms a 1:1 complex with lipase
The lid part of the protein shifts making the active site available, which also shift the β5 loop (changes conformation), an oxyanion hole is created and a hydrophobic surface near the active site.
It can now accommodate the hydrophobic molecule so the reaction can take place

Question 14

Describe phospholipase A2 (PLA2)?

Answer 14

An enzyme that releases fatty acids from the second carbon group of a phospholipid
Phospholipase A2 contains a hydrophobic channel that gives the substrate direct access to the enzyme’s active surface
Conformational change is not required for catalysis
They produce lysophospholipids: powerful detergents – help to emulsify other lipids, aiding digestion

Question 15

How are lipids absorbed?

Answer 15

Bile acid micelles transport non-polar lipid products across the aqueous boundary of the intestinal wall
Inside the cell
Fatty acids then form complexes with intestinal fatty-acid binding protein (I-FABP) to increase their solubility and protect the intestinal cells from their detergent properties

Question 16

What is also required in absorption of lipids?

Answer 16

Lipoprotein lipase on external surface of capillary epithelial cell membrane catalyses the hydrolysis of triacylglycerols to fatty acids and mono-acylglycerols
These cross the epithelial cell membranes and are then either metabolised for energy or converted back to triacylglycerols for storage

Question 17

How are lipids transported in general?

Answer 17

They are transported as lipoproteins (protein-lipid complex)
They are globular micelle-like particles containing:
Hydrophobic interior: Cholesterol esters and Triacylglycerols
Amphiphilic exterior: Protein(s), Phospholipids and cholesterol (wrapped around the interior)

Question 18

How are chylomicrons formed?

Answer 18

They carry dietary lipids to the circulation, after digestion and absorption

Triacylglycerols are reformed in the smooth ER
apoB-48 is synthesised in the rough ER (enzyme)
Chylomicron assembly occurs in both the ER and Golgi
They contain triacylglycerols, phospholipids and cholesterol
Chylomicrons are released into the lymph system, then into blood

Question 19

What are the different types of lipoproteins? what do they transport?

Answer 19

Chylomicrons - dietary lipids to tissues
Very low density lipoproteins (VLDL) - endogenously synthesised lipids to tissues
Intermediate density lipoproteins (IDL) - endogenously synthesised lipids to tissues
Low density lipoproteins (LDL) - cholesterol to tissues
High density lipoproteins (HDL) - cholesterol to the liver

They have different characteristics: density correlates with size and protein content – smaller lipoproteins contain more protein and have higher density

Question 20

What are the protein component part of lipoproteins?

Answer 20

Apolipoproteins
There are many types e.g. • ApoB-100 – structural (required for particle assembly)
It also binds to LDL receptor and is very hydrophobic, other apolipoproteins are water soluble, but associate weakly with lipoprotein

Apo A-I - found mainly in HDL
It has 4 monomers, mainly helical, with proline induced kinks every 22 residues (makes a figure of 8 shape)
Due to amino acid residues giving distinct polar and non-polar sections to helix, it can wrap around HDL

Question 21

Give an overview of delivery of lipids to peripheral tissues?

Answer 21

Chylomicrons delivery dietary triacylglycerols to muscle and adipose tissue, and dietary cholesterol to the liver - the triacylglycerols are hydrolyzed through the action of the extracellular enzyme lipoprotein lipase
Remnants of chylomicrons (containing mainly dietary cholesterol) are taken up by the liver
VLDL deliver endogenously synthesised triacylglycerols in the same way, shrinking to become first IDL, then LDL (containing mainly cholesterol)

Question 22

Describe cholestrol uptake from LDL?

Answer 22

In mainly the liver, adrenals, & adipose tissue

Receptor-mediated endocytosis
apoB-100 binds to LDL receptors
The receptors cluster into clathrin-coated pits into the cells creating vesicles (they invaginate) to form clathrin-coated vesicles
They then fuse with endosomes (pH 5), where the LDL particle dissociates from its receptor - the LDL receptors recycled
The endosome fuses with a lysosome
Cholesterol released - converted to cholesterol esters for storage

Question 23

Describe HDL’s function?

Answer 23

HDL transports excess cholesterol from tissues back to the liver for disposal
Maturation process – lipid-poor apoA-1 picks up cholesterol and phospholipids from extra hepatic tissues via ABCA1 transporters
Other transporters can help e.g. Phosphatidyl choline
Cholesterol is esterified by LCAT (lecithin cholesterol acyl transferase) enzyme, producing mature HDL particles with high cholesterol ester content