Identify and describe the three different classes of lipids
- Fatty acid derivatives – fatty acids and triacylglycerol
- Hydroxy-methyl-glutaric acid derivatives – ketone bodies, cholesterol
- Vitamins – ADEK
Explain how energy storage varies between a healthy and obese man
Describe the structure of triacyglycerol
Triacylglycerols are hydrophobic
Describe the storage of TAG
- Stored in an anhydrous form
- Stored in adipose tissue
- Storage / mobilisation under hormonal control
Identify three circumstances where triacylglycerols are used
- Prolonged exercise
Identify the tissues involved in triglyceride metabolism and illustrate their role
Where does stage 1 of TAG metabolism occur?
Gastrointestinal tract (extracellular)
What occurs in stage 1 of TAG metabolism?
- Extracellular hydrolysis of dietary lipids (TAG) in small intestine by pancreatic lipases
- Fatty acids and glycerol are formed
In 5 steps, describe what happens in TAG metabolism after absorption in to the GI tract
⇒ Converted back to triglycerides in GI tract
⇒ Packaged into lipoprotein particle (chylomicrons)
⇒ Released into circulation via lymphatics
⇒ Carried to adipose tissue
⇒ Stored as triglyceride
Describe fat mobilisation
- Fatty acids are released when needed
- They are carried to tissues as albumin-fatty acid complex
Fat mobilisation is under hormonal control.
- Increases with glucagon/adrenaline
- Decreases with insulin
Which consumer tissues are fatty acids not mobilised to?
- Cells without mitochondria e.g. RBC
- Brain; fatty acids do not easily pass blood-brain barrier
In 5 steps, describe and illustrate the triglyceride/fatty acid cycle in adipose tissue
1 – Glucose transport
2 – Glycolysis
3 – Esterification
4 – Lysis
5 – Re-esterification
What causes the release of fatty acids as alternative fuel?
Low extracellular [glucose]
Describe the molecular structure of fatty acids
Amphipathic: contain hydrophilic & hydrophobic groups
What are the two types of fatty acids?
- Saturated: no double bonds between neighbouring C-atoms
- Unsaturated: 1/more double bonds between neighbouring C-atoms
Where does stage 2 of fatty acid metabolism occur?
In three steps, describe what occurs in fatty acid catabolism
⇒ FA is activated outside the mitochondrion
⇒ FA is transported across the inner mitochondrial membrane using a carnitine shuttle
⇒ FA cycles through sequence of oxidative reactions, with C2 removed each cycle
Fatty acid activation occurs outside the mitochondria, in the cytoplasm.
Describe how this occurs
- Activated by linking to coenzyme A by the action of fatty acyl CoA synthase
- Activated fatty acids (fatty acyl~CoA) do not readily cross the inner mitochondrial membrane (carnitine shuttle)
Carnitine shuttle transports fatty acyl~CoA across the mitochondrial membrane.
Describe how and why this process is regulated
- Regulated, so controls the rate of FA oxidation
- Inhibited by malonyl~CoA (biosynthetic intermediate)
Fatty acid catabolism is also called β oxidation.
Identify three key features of this process
- H+ and e- transferred to NAD+ and FAD
- Stops in absence of O2
- No ATP synthesis
Briefly describe glycerol metabolism
Glycerol can be transported in the blood to the liver, where it is metabolised
Acetyl-CoA is the main convergence point for catabolic pathways.
What is its function?
Acetyl~CoA is the most important intermediate in both catabolic and anabolic pathways
Three ketone bodies are produced in the body.
What are they?
- Acetoacetate: CH3COCH2COO- (liver)
- Acetone: CH3COCH3
- β-hydroxybutyrate: CH3CHOHCH2COO- (liver)
Describe the physiological and pathological variation in the plasma concentration of ketone bodies
- Normal < 1 mM
- Starvation = 2-10 mM (physiological ketosis)
- Untreated Type 1 diabetes > 10 mM (pathological ketosis)
Briefly outline the pathways in which ketone bodies are synthesised by liver mitochondria
How is acetone formed?
Acetone is formed from the spontaneous (non-enzymatic) decarboxylation of acetoacetate
Explain how ketone body production is controlled in the liver
Outline the pathways involved in ketone metabolism
Explain how ketone bodies synthesis is regulated by the insulin:glucagon ratio in fed and starvation states
- Fed state: high insulin:glucagon inhibits lyase and activates reductase → cholesterol synthesis
- Starvation state: low insulin:glucagon inhibits reductase and activates lyase → ketone body synthesis