Phospholipid biosynthesis

What are the main families of phospholipid?

Phosphoglycerides, sphingolipids, Sterols

What is the general structure of phosphoglycerides?

Two fatty acyl chains esterified to glycerol-3-phosphate

What structure do the fatty acyl chains usually have in phosphoglycerides?

Chain 1 is usually saturated, chain 2 is usually unsaturated

What phosphoglyceride has a H R-group?

Phosphatidic acid (PA)

What phosphoglyceride has a choline R-group?

Phosphatidylcholine (PC)

What phosphoglyceride has a ethanolamine R-group?

Phosphatidylethanolamine (PE)

What phosphoglyceride has a serine R-group?

Phosphatidylserine

What phosphoglyceride has a inositol R-group?

Phosphatidylinositol

What intermediate is required for the synthesis of phosphoglycerides?

Phosphatidate

How can Phosphatidate be synthesised?

Synthesised in ER of cells from glycerol-3-phosphate

What must happen to Phosphatidate or the group to be added for phospholipid synthesis to occur?

One must be activated

How is glycerol-3-phosphate converted to Phosphatidate?

Acyl CoA adds fatty acyl chains to glycerol-3-phosphate, catalysed by acyl transferase

How is Phosphatidate acivated?

Cytidine triphosphate reacts with the Phosphatidate molecule, forming CDP-diacylglycerol.
This molecule can then react with the head group, forming the phospholipid

How can the head group of a phosphoglyceride be activated?

Head group reacts with ATP, forming phosphoryl-head group.
Then reacts with CTP, forming CDP-head group.
The CDP-head group can then react with the diacylglycerol molecule

What is the major route of phosphatidylcholine (PC) synthesis?

Via dietary choline activation

What is the minor route of phosphatidylcholine (PC) synthesis?

Synthesised in the liver by the methylation of phosphatidylethanolamine (PE) head group.
Occurs when dietary choline is insufficient

How can phosphatidylcholine be produced from dietary choline?

Choline converted to choline-phosphate then to CDP-choline.
Added to DAG to form PC.
Catalysed by CK, CCT, and CPT

What is the limiting step in the synthesis of phosphatidylcholine from choline?

Formation of CDP-choline, action of CCT is controlled by the membrane itself

How can phosphatidylserine (PS) be synthesised?

Synthesised by base-exchange reactions from phosphatidylcholine (PC) or phosphatidylethanolamine (PE)

Where is phosphatidylcholine found in the membrane?

~50% of membrane mass.
80-90% of the membrane outer leaflet is PC

What is the importance of phosphatidylcholine in the membrane?

Important for membrane structure and integrity.
Precursor of DAG signalling

Where is phosphatidylethanolamine found in the membrane?

15-25% of total phospholipids in mammals, mostly found on the inner leaflet

How is phosphatidylethanolamine synthesised?

Ethanolamine converted to phosphoethanolamine, then to CDP-ethanolamine and added to DAG.
Catalysed by EK, ECT, EPT

What are the functions of phosphatidylethanolamine?

Precursor for PC synthesis.
Substrate for PTMs.
Influences membrane topology.
Promotes cell and organelle membrane fusion

Where is phosphatidylserine found in the membrane?

5-15% of phospholipids in mammals, higher distribution in the inner leaflet of the membrane

What are the roles of phosphatidylserine?

Activator of PKC, exposure to surface contributes to platelet aggregation and elimination of apoptotic cells

What can be formed by the phosphorylation of phosphatidylinositol?

phosphatidylinositol phosphates (PIPs)

What is the function of phosphatidylinositol?

Roles in lipid signalling, cell signalling, and membrane trafficking

What is the most common fatty acid composition of phosphatidylinositols?

Chain 1 is usually stearic acid;
Chain 2 is usually arachidonic acid

What are alkyl-acyl-glycerophospholipids?

Phosphoglycerides containing an alkyl chain ether-lined to carbon 1 of glycerol

What can alkyl-acyl-glycerophospholipids be oxidised to form?

Vinyl ethers=70% of myelin.

What is is glycerol replaced by in sphingolipids?

Sphingosine

What is the structure of sphingosine?

Amino alcohol with a long hydrocarbon chain

Where are sphingolipids found?

Highest concentration in CNS, on outer leaflet

Where are phospholipids synthesised?

ER membranes

How are phosphatidylcholines moved to the outer leaflet of the membrane?

Flipped by flippase enzymes