Metabolism S5 - Lipid transport and by-products of energy production Flashcards
Why are lipids associated with proteins in the blood?
They are insoluble in water
What are the two methods of lipid transport in the blood?
Lipoproteins or albumin (less than 2%)
Lipoprotein disorders are associated with what main clinically important disease?
Atherosclerosis
What is the general structure of lipoproteins?
Hydrophilic surface coat - apoproteins, cholesterol and phospholipids
Hydrophobic core - TAGs, Cholesterol esters
How is the structure of lipoproteins maintained?
LCAT convert cholesterol to cholesterol esters when core is removed to maintain shape
What structural role do apoproteins play?
- Involved in packaging non-water soluble lipids into soluble form
- This is possible as they contain a hydrophobic region that interacts with the lipid molecule and hydrophilic region that interacts with water
What functional role do apoproteins play?
- May be involved in activation of enzymes
- Recognition of cell surface receptors
- Transport of lipids
What do chylomicrons transport and to which destination?
TAGs
Intestine to adipose tissue
What do VLDLs transport and to which destination?
TAGs
Liver to adipose tissue
What do LDLs transport and to which destination?
Cholesterol
Liver to tissue
What do HDLs transport and to which destination?
Cholesterol
Tissues to the liver
All cells (except red blood cells) are able to synthesise _______ from acetyl CoA and could satisfy their requirements by biosynthesis. In practice, all cells appear to prefer the uptake of ________ ________ circulating in plasma _________
Cholesterol
Pre-formed cholesterol
Lipoproteins
Tissues obtain the _______ they need from LDLs by the process of _______ ________ _______. LDL particles are taken up by the cell and the cholesterol released inside the cell
Cholesterol
Receptor mediated endocytosis
Outline receptor mediated endocytosis of cholesterol
- Cells requiring cholesterol synthesise LDL receptors that are exposed on the cell surface
- These receptors recognise and bind specific apoproteins (Apo B100) on the surface of the LDL
- The LDL receptor with its bound LDL is then endocytose by the cell and subjected to lysosomal digestion
- Cholesterol can be stored (as cholesterol esters) or used by the cell
- This also inhibits the synthesis of cholesterol by the cell and reduces the synthesis and exposure of LDL receptors.
- This prevents the cell from accumulating too much cholesterol
Describe Type III hyperlipoproteinaemia
- Raised LDL and chylomicron remnants
- Associated with coronary artery disease
- Caused by defective apoprotein E
Describe Type IV hyperlipoproteinaemia
- Raised VLDLs
- Associated with coronary artery disease
- Defect unknown
Describe Type V hyperlipoproteinaemia
- Raised chylomicrons and VLDL in fasting plasma
- Associated with coronary heart disease
- Defect unknown
What type hyperlipoproteinaemia is familial cholesterolaemia
IIa
List some treatments for hyperlipoproteinaemia
- Reduce cholesterol and TAGs in the diet
- Statins: inhibits HMG-CoA reductase to prevent cholesterol synthesis from acetyl-CoA
- Bile Salt sequestrants: lower cholesterol by increasing its disposal from the body. They bind to the GI tract preventing them from being reabsorbed into the hepatic-portal circulation and promoting their loss in faeces
Describe two mechanisms by which tissues can obtain lipids from lipoproteins
1) Lipoprotein lipase - Removes core TAGs from lipoproteins to produce fatty acids and glycerol, found attached to inner surface of capillaries in adipose tissue
2) Receptor mediated endocytosis - LDL binds to LDL receptors on surface membrane and complex is taken up in cell
How are superoxide radicals produced in the cell?
0.1-2% of electrons are leaked from the electron transport chain before they reach the end of the chain and prematurely reduce oxygen in the mitochondria
List 3 reactive oxygen species
1) Hydroxyl radical
2) Nitric oxide
3) Peroxynitrite (formed from nitric oxide and oxygen reacting together
Which ROS has an important role in inflammation/
Peroxynitrite
Outline cellular defences against ROS
- Superoxide dismutase + catalase
- NADPH and glutathione
- Antioxidant vitamins
- Flavonoids and vitamins
How is superoxide dismutase used as a cellular defence against ROS?
- SOD catalyses the reaction of superoxide radicals together to form water + hydrogen peroxide
- However hydrogen peroxide os a ROS
- Catalase rapidly breaks hydrogen peroxide down to water and oxygen
The reaction of unsaturated lipids with ROS forms ______ ______. This damage to cell membranes is thought to be involved in the early stage of cardiovascular disease.
lipid peroxides
What is hyperlipoproteinaemia?
Any condition in which, after a 12 hour fast, the plasma cholesterol and/or plasma triglycerides are raised
List signs or symptoms of very high blood cholesterol
- Corneal arcus
- Xanthelasma and/or tendon xanthoma
- Accelerated development of atherosclerotic diseases
Outline two pathways by which tissues can obtain the cholesterol they need
1) Direct synthesis of cholesterol from acetyl CoA within tissues
2) Receptor mediated endocytosis of LDL particles
What cells are capable of oxidative burst?
Neutrophils and monocytes
Name two enzymes involved in defences against ROS
Superoxide dismutase
Catalase
What is oxidative stress?
- Occurs when the production of ROS is excessive and anti-oxidant levels are low
- Underlies pathology of atherosclerosis, Parkinson’s and Alzheimers’s
What are the potential problems of a low-fat diet?
Need fats for cellular components such as lipid membranes as well as signalling molecules
Name two anti-oxidant vitamnins
Vitamin E
Vitamin C
Briefly explain how a respiratory burst is produced by monocytes and neutrophils
- Produced by a membrane-bound enzyme complex termed NADPH oxidase
- It transfers electrons from NADPH across the membrane to couple these to molecular oxygen to generate superoxide radicals
