BMP: Lipid digestion Flashcards
1
Q
What is the most abundant form of lipids.
What are these?
A
Triglycerides (TAG)
Fatty acid triesters of glycerol
2
Q
What is the primary storge of metabolic energy?
A
TGs
3
Q
How are TGs digested/absorbed?
A
- Pancreatic lipase is secreted in the duodeum and hydrolyses TAG at positions C1 and C3, liberating two fatty acids.
- The free fatty acids and 2-monoacylglycerol is absorbed by the intestinal epithelium.
- Absorption of hydrophobic, free fatty acid is facilitated by assimilation within micelles formed by bile salts eg cholate.
4
Q
- What are lipoproteins composed off?
- What do they do?
- What classes are there and what are these base on
A
- Protein, TGs and Cholesterol
- Transport lipids in the aqeuous eniroment of the blood
- 4 major classes of lipoproteins defined by density and size
- CM (chylomicron)
- VLDL (very low density lipoprotein)
- LDL (low density lipoprotein)
- HDL (high density lipoprotein)
5
Q
- What are lipoprotein particles produced by?
- What are they made of?
- Describe the structure
A
- Hepatocytes and enterocytes
- TGs, cholesterol, apolipoprotinens and phospholipids
- The hydrophobic TAG and cholesteryl esters make up the centre. Apolipoprotein strands, cholesterol molecules and phospholipids are located in the outer shells
6
Q
What are the differences between VLDL and HDLs?
A
Hepatocytes assemble VLDLs and HDLs, and they are distinguishable from each other by their differences in size, density, lipid composition and apolipoprotein content.
7
Q
What are the functions of apolipoproteins?
A
- Structural component of lipoprotein particle
- Emulsify the lipoprotein particle to make it more stable in aqueous solution for carriage in blood
- Ligands for cell surface receptors
- Interact with cellular receptors that determine how and where lipoprotein particles are metabolised.
Each lipoprotein particle has a specific set of
8
Q
What are the different isoforms of apolipoprotein and their respective functions?
A
Different apolipoprotein isoforms
- Apo A - present in HDLs. Binds to cellular receptors mediating the efflux of cholesterol from peripheral cells, and the influx of cholesterol into hepatocytes
- Apo B - encourages cellular uptake of LDL
- Apo C - synthesised in the liver and is a peripheral activator of lipoprotein lipase (LPL)
- Apo E – essential for metabolism of lipoprotein.
9
Q
What happens to the absorbed FAs?
A
- They are converted back into TAG within the intestinal epithelium
- TAG is then packaged into chylomicrons and exocytosed into the intestinal lymphatic vessels then into the large body veins via thoracic duct
- The chylomicrons pass through the blood to peripheral tissue. Particularly skeletal muscle and adipose tissue - white/brown.
- Endothelial capillary cells contain cell surface receptors which bind chylomicrons.
- The chylomicron TAG components are hydrolysed by action of extracellular lipoprotein lipase. The tissue accumulates the liberated fatty acid and 2-monoacylglycerol.
10
Q
What happens to the chylomicron remenants?
A
- •During passage through tissues, chylomicrons progressively lose TAG.
- •They shrink to form small, cholesterol enriched chylomicron remnants (50 nm).
- •These remnants remain in the blood and are delivered to the liver where they are endocytosed.
- •Therefore, chylomicrons and their remnants deliver dietary TAG to muscle and adipose tissue and dietary cholesterol to the liver.
11
Q
Discuss the function and movement of VLDL
A
- •VLDL (50 - 100 nm)are synthesised in liver, transporting endogenous TAG and cholesterol to peripheral tissues.
- •VLDL’s are degraded by lipoprotein lipase in adipose tissue and muscle.
- •After progressively losing TAG VLDL’s are converted into IDL/LDL (20 - 30 nm) which return to the liver.
- •LDL commonly sheds cholesterol esters along arterial walls.
- •Biochemical basis for atherosclerotic plaque development.
12
Q
Describe LDL and the atherogenic events
A
- •LDL carry the majority of the cholesterol in the blood
- •Capable of moving into the vessel wall
- •LDL becomes oxidized (oxLDL) by free radical molecules
- Proteins and lipids undergo oxidative changes forming complex products.
- Extensive alteration of protein composition and structure
- Changes in amino acids
- Proteolysis & cross-linking of apo B
- oxLDL is avidly scavenged & degraded by macrophages
- Foam cell formation
- •Triggers cascade of immune responses
- •Formation of atheroma
- Eventual rupture
13
Q
- Describe function of HDL
- How is HDL assembled?
A
- •HDL (5 - 20 nm) has an opposite function to LDL. The HDL removes cholesterol from the tissues for transmission to the liver.
- HDL is assembled in the blood from components obtained through degradation of other lipoproteins.
14
Q
- What does TAG accumulation in adipocytes result from?
- What happens when TAG intake increases?
- What can happen to these adipocytes?
A
- •TAG accumulation in adipocytes results from excess fat intake
- –carbohydrate derived fatty acid being relatively insignificant.
- •Increased TAG intake increases white adipose tissue, both increasing cell number and cell size.
- •Once formed adipocytes can substantially swell or shrink, but are rarely lost hence can act as ‘fat sponges’.
15
Q
Describe leptin resistance in terms of obesity
A
- •Obesity in humans is partly due to ‘leptin resistance’ perhaps due to decreased receptor level/activity.
- •Diminished response to leptin results in elevated neuropeptide Y secreted from the hypothalamus (controlled by ghrelin).
- •Neuropeptide Y stimulates appetite and promotes insulin secretion, leading to TAG accumulation.
- •The leptin/ghrelin signalling pathway may offer potential for therapeutic intervention, although obesity has a multifactorial nature.
