Lecture 18 - Synthesis of lipids

Question 1

Define and name the 3 goups of lipids?

Answer 1

Lipids - A diverse group of naturally occurring molecules that are soluble in non-polar organic solvents such as chloroform (insoluble or poorly soluble in water). Their structure varies.

Lipids can either be:
* Neutral - (storage) Triacylglycerols
* Polar - (often structural) Phospholipids
* Steroids - Cholesterol
The are esters of long chain fatty acids

Question 2

What are fatty acids

Answer 2

Composed of a carboxyl head group and a hydrocarbon tail. The hydrocarbon tail is where the structure varies. They can be different lengths or either saturated (No Carbon carbon double bonds) or unsaturated (contain carbon double bonds)

Question 3

Describe the process of fatty acid synthesis?

Answer 3

Fatty acid synthesis takes place in the cytosol however requires acetyl CoA.
1. Acetyl CoA is used through carboxylation to form malonyl CoA as well as forming acetyl ACP (acetyl carrier protein)
2. The malonyl CoA then becomes malonyl ACP due to the action of a transferase
3. The malonyl ACP (carbon donor) and acetyl ACP then react in a condensation reaction to form acetoacetyl ACP (C4)
Second stage of cycle
1. This is then reduced to form D-3-hydroxybutyryl ACP
2. This is then dehydrated to form crotonyl ACP
3. This is then reduced to butyryl ACP
4. This is then reacted in a condensation reaction with malonyl ACP to form β-ketoacyl ACP (C6)
The second stage of the cycle is then repeated with the β-ketoacyl ACP using malonyl ACP still as the carbon donor until C16-acyl ACP is formed.
This then becomes Palmitate the end point

Question 4

What is the acetyl shuttle?

Answer 4

The acetyl shuttle
The acetyl shuffle is used in order to allow acetyl CoA to leave the mitochondria and reach the cytoplasm.
1. Acetyl CoA is first reacted with oxaloacetate to form citrate using the enzyme citrate synthase. He citrate is able to move through the mitochondrial membrane.
2. Once in the cytoplasm citrate lyase catalyses the reaction to reform acetyl CoA and oxaloacetate in the cytoplasm.
Oxaloacetate then goes on to form malate and then pyruvate with can be transported back into the mitochondria. Inside the mitochondria the pyruvate can form oxaloacetate.

Question 5

How is malonyl CoA produced in fatty acid synthesis?

Answer 5

Malonyl CoA production

Acetyl CoA (C2) + ATP + HCO3- —-> Malonyl CoA (C3) + (ADP …)
Acetyl CoA carboxylase (RATE LIMITING STEP)

Acetyl CoA + ACP —> acetyl ACP + CoA
Acetyl transferase

Malonyl CoA + ACP —> malonyl ACP + CoA
Malonyl transferase

Question 6

Describe the subsequent steps of fatty acid synthesis from malonyl production.

Answer 6

Condensation
The enzyme β-ketoacyl synthase catalyses the condensation of Acetyl ACP and Malonyl ACP to form Acetoacetyl ACP.

Reduction 1
β-ketoacyl reductase catalyses the reduction of aceto-acyl ACP to D-3-Hydrobutyryl ACP

Dehydration
Dehydratase catalyses the dehydration of D-3-Hydroxybutryl ACP to Crotonyl ACP

Reduction 2
Enoyl reductase catalyses the reduction of Crotonyl ACP to Butyryl ACP

Palmitate Formation
C16-acyl ACP through the action of the enzyme thioesterase which removes the ACP to form palmitate

Each turn of the cycle adds 2 C to the C6-β-ketoacyl ACP which means in total the cycle needs 7 turns to form palmitate.
8acetyl CoA + 7ATP + 14NADPH –> palmitate + 14 NADP+ + 8CoA + 6H2O + 7ADP + 7Pi

Long chain fatty acids - elongate further than C16
* Enzymes on cytosolic face of ER membrane
* 2C added at a time to carboxyl end of the fatty acid
* Driven by decarboxylation of malonyl CoA (donor)

Unsaturated fatty acids
Fatty acid desaturase insert cis Δ9 double bond

Question 7

How is fatty acid synthesis regulated?

Answer 7

1. Irreversible reaction rate limiting step by Acetyl-CoA carboxylase
   Hormones such as insulin and glucagon affect kinase enzymes with cause phosphorylation.
2. Allosteric regulation by reactants and products
3. Adaptive control