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Lecture notes of 11 pages for the course Metabolic Pathways at QMUL
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Ketone body formation & fatty acid synthesisLearning objectives:
1. Compare and contrast fatty acid degradation and synthesis
2. Explain and describe fatty acid degradation and synthesis regulation
3. Describe in detail the pathway of fatty acid synthesis
4. Structure and function of the multifunctional enzyme complex fatty acid synthetase
5. Role of oxaloacetate in fatty acid synthesis
6. Source of NADPH, the reducing power for fatty acid synthesis
7. Chain elongation and desaturation
8. Essential fatty acids
What happens to the acetyl coA formed from fatty acids?
Enter the citric acid cycle to aerobically degrade and produce ATP
However, acetyl coA will only enter if fat and carbohydrate degradation are appropriately balanced
- Need carbohydrate catabolism to get proper fatty acid catabolism
Entry of acetyl coA into citric acid cycle is dependent on the availability of oxaloacetate (for citrate production)
- We know it from? 1st step of gluconeogenesis pyruvate reacts to form oxaloacetate using pyruvate carboxylase
Thus if concentration of oxaloacetate becomes low (because used up in gluconeogenesis) in say starvation or
diabetes conditions the acetyl coA cannot enter citric cycle
Instead the acetyl coA form ketone bodies
Ketone body formation
Under starvation conditions acetyl coA is converted into:
1. acetoacetate
2. D-3-Hydroxybutyrate Ketone bodies
3. Acetone
Sum reaction:
- 2 acetyl coA + H2O acetoacetate + 2CoA + H+
1. 2 molecules of acety coA condense (reverse of thiolysis in β-oxidation- catalyst thiolase)
2. Condensation reaction adds water & acetyl (similar to citrate synthase reaction –HMG CoA synthase)
- Favourable due to hydrolysis of thioester linkage
3. HMG-CoA lyase
4. Acetoacetate can then either be converted to D-3-Hydroxybutyrate (enzyme catalysed and limited by how much
NADH available) or acetone (slow and spontaneous process- good test for diabetes)
Ketone bodies as a fuel source
The liver is the major source of ketone bodies
Ketone bodies are transported in the blood to other tissues
Ketone bodies are a water soluble equivalent of acetyl-CoA units
Acetoacetate in the tissues
Acetoacetate is first activated to acetoacetate by transferring the CoASH by a thiolase reaction
Some tissues, such as cardiac muscle preferentially use ketone bodies
The brain can use ketone bodies under starvation conditions for long term starvation
, Summary
Even though the citric acid cycle intermediate oxaloacetate can be used to synthesis glucose, acetyl-coA cannot be
used to synthesis oxaloacetate
The 2 Cs enter the citric acid cycle as acetyl-CoA leave as CO 2
1.COMPARE AND CONTRAST FATTY ACID DEGRADATION AND SYNTHESIS
Fatty acid metabolism overview
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