Lipid Synthesis and Degradation Flashcards
Describe the importance of fats as an energy store
Fats are synthesised and stored when our calorific intake exceeds the immediate needs of the body
The energy content of fat per gram is over twice that of either carbohydrate or protein
1g fat - 37kjoules
1g protein - 17kjoules
1g carbohydrate - 16kjoules
Describe fatty acid synthesis and storage
Fats are often made from dietary carbs, but some a.as can also be used
Not all fats are stored as they are also the preferred energy source for cardiac muscle
Fats are stored in adipose tissue as TGs and most are synthesised in the liver
Takes place in the cytosol and requires: Acetyl-CoA, NADPH, ATP
It involves the sequential addition of 2 two carbon units derived from acetyl-CoA
How is acetyl CoA transported into the cytosol from the mitochondria?
Needs a Citrate-malate antiporter
Acetyl CoA reacts w oxaloacetate to give citrate. Citrate is then transported out the mitochondria into the cytosol where the ActetylCoA and oxaloacetate is regenerated.
Oxaloacetate–> malate–> pyruvate, forming NADPH
Pyruvate then is transported back into the mitochondria, where it is converted to oxaloacetate, and the cycle repeats.
Describe the 1st step of fatty acid synthesis
Outline the steps of fatty acid synthesis
(dont need to know the diagram in detail)
Acetyl co a forms malonyl coA which forms malonyl ACP
Hay a series of condensation, reduction and dehydration reactions to form a C4 molecule called Butyryl ACP
malonyl ACP combines w Butyryl ACP to form a fatty acid
Fatty acid synthesis is catalysed by Fatty Acid Synthase complex.
What is fatty acid synthase?
The protein responsible for fatty acid synthesis is called fatty acid synthase
This is a multienzyme complex that covalently links the substrate and the enzyme active site using ACP (Acyl Carrier Protein).
This enables the growing fatty acid chain to be passed from one active site to the next.
The enzyme exists as a dimer arranged head to tail, which also increases reaction efficiency
Briefly summarise fatty acid synthesis
Describe fatty acid degradation
Fatty acids are stored as TGs mainly in adipose tissue
To be degraded, the triglycerides must first be mobilised and transported to the liver, where they’re activated in the cytosol
The activated triglycerides are then degraded in the mitochondria of the hepatocytes
Describe fatty acid mobilisation
Before degradation, fatty acids must be mobilised from TGs and stored in adipocytes
Adrenaline/glucagon stimulate a Gs-coupled receptor, which activates AC–> cAMP–>PKA
PKA activates TAG lipase. TAG lipase converts triacylglyceride to diacylglyceride
Other lipases then break down DAG into glycerol and free fatty acids
How are fatty acids transported to mitochondria?
After mobilisation, FA are transported to the liver where they produce acyl CoA
Acyl CoA–> acyl carnitine, which is transported into the mitochondrial matrix
Transport of acyl carnitine into the matrix is inhibited by malonyl CoA, to prevent synthesis and degradation occurring simultaneously
In the matrix, acyl carnitine reacts with CoA to reform acyl CoA, which can then be oxidised
Carnitine deficiency can cause muscle weakness/death bc it prevents acyl CoA from entering the mitochondrial matrix
What is fatty acid oxidation
Fatty acid oxidation is the reverse of fatty acid synthesis – it produces acetyl CoA. FADH2 and NADH which can enter the ETC and make ATP
- Acyl CoA is first oxidised, producing FADH2
- The intermediate is hydrated and oxidised again, producing NADH
- The intermediate produced then undergoes thiolysis to form acetyl CoA
When does fatty acid oxidation take place?
Fatty acid oxidation occurs when little glycolysis is taking place – this prevents acetyl CoA entering the TCA cycle as not enough is being produced
Compete oxidation to palmitate (a fatty acid) yields 106 ATP – this is a lot compared to glucose
Describe ketogenesis
FA oxidation produces acetyl CoA, which can enter ketogenesis to produce ketone bodies- an alternate energy source
In the liver, v little acetylCoA is needed to meet metabolic demands (as they are satisfied from elsewhere), so acetyl CoA undergoes ketogenesis
Acetyl CoA is first converted to acetoacetyl CoA, which is then converted to HMG-CoA. This is converted to acetoacetate
Acetoacetate is then reduced to hydroxybutyrate or acetone
What happens to ketone bodies?
Ketone bodies are produced in the liver. They can then be exported into the circulation and carried to tissues, where they are used as energy
Cardiac muscle and the renal cortex use ketone bodies as their preferred energy source
During starvation, when glucose is depleted, ketone bodies become a major source of energy for the brain
What happens to glycerol from the breakdown of TGs?
Breakdown of triglycerides gives acetyl-CoA and glycerol
In the liver glycerol is used to synthesise glucose by gluconeogenesis
In the muscle glycerol is used in glycolysis and oxidative phosphorylation to produce ATP
