Membrane synthesis Flashcards
How are cell membranes synthesised?
The hydrophobic nature of the lipids means lipids are poorly soluble in the aqueous interior of a cell – presents a challenge
They are synthesised by the expansion of existing membranes
Early steps take place in the cytoplasm producing water soluble intermediates - incorporated into the amphipathic regions
Final steps are through enzymes bound to pre-existing membranes (SER membranes)
Enzymes required are present on the organelles to which the membrane it is being synthesised for
Products are incorporated into membranes as they are generated
What must happen once membranes are formed?
Membranes are continuously renewing their molecules - as well as vesicles transporting membranes
Once formed membrane lipids must be:
- Delivered to the correct leaflet of the bilayer
- Distributed to membranes of organelles
- Distributed to the plasma membrane
Where is the site of membrane synthesis?
They are primarily synthesised in the smooth endoplasmic reticulum
Produces cholesterol & membrane phospholipids using enzymes embedded in its smooth membranes
Produces more membranes for itself or can transport newly made lipids to their ultimate cellular destinations
Some lipids are synthesized in association with other organelle membranes, (see later example) but most are synthesized in the SER
What is the start of membrane synthesis?
Starts with fatty acid synthesis
Key components of phospholipids and sphingolipids
New fatty acids can also be used to anchor proteins to membranes (lipidation)
Major fatty acids in phospholipids contain 14, 16, 18 or 20 carbon atoms.
Include both saturated and unsaturated fatty acid chains
Fatty acid chains of sphingolipids - are longer in sphingolipids than glycerophospholipids (can contain up to 26 carbon atoms)
What are the stages of fatty acid synthesis?
First stage - acetyl-CoA production
Second stage - conversion of acetyl-CoA to Malonyl-CoA
Third stage - production of palmitate
What is involved in the production of acetyl-CoA?
Catalysed by Fatty acid synthase (FAS)
FAS: multi-enzyme protein
Creation of fatty acids from acetyl-CoA and NADPH
Takes place in the cytoplasm
Most of the acetyl-CoA which is converted into fatty acids is derived from carbohydrates via the glycolytic pathway
Describe stage 1 of fatty acid synthesis - acetyl-coA production?
- Conversion of pyruvate to acetyl CoA - each pyruvate molecule loses one carbon atom with the release of carbon dioxide
Pyruvate is transported into the mitochondrion using a transport protein - During pyruvate breakdown, electrons are transferred to NAD+ to produce NADH, which will be used by the cell to produce ATP
- In the final stage of the breakdown of pyruvate, the acetyl group is transferred to Coenzyme A to produce acetyl CoA
Describe stage 2 of fatty acid synthesis - malonyl-CoA production?
One molecule of acetyl-CoA joins with a molecule of bicarbonate, requiring energy rendered from ATP
Reaction is irreversible - committed step in fatty acid synthesis
Describe stage 3 of fatty acid synthesis - palmitate production?
Acetyl-CoA + 7x malonyl-CoA + 14 NADPH
Makes palmitate and releases 14x NADP and 7x CO2
Catalysed by fatty acid synthase (FAS)
Describe palmitate?
This is the main product of the FAS system and is the precursor for other long-chain fatty acids
When the chain reaches 16 carbons palmitate (16:0) leaves the cycle
Palmitoyl protein thioesterases: remove thioester-linked fatty acyl groups from modified cysteine residues (allowing it to be a precursor into other molecules)
Palmitate precursor = saturated
Can be lengthened to form stearate (18:0) or longer saturated fatty acids by further additions of acetyl groups
Occurs through the action of fatty acid elongation systems present in the SER and the mitochondria
How are unsaturated fatty acids produced from palmitate?
Desaturase enzymes: remove two hydrogen atoms from a fatty acid, creating a carbon/carbon double bond
How are fatty acids incorporated into phospholipids on the SER membrane?
Enzymes on the cytosolic face of the SER link fatty acids, Glycerol 3-phosphate and polar head group precursors
These are then inserted into the SER membrane
Phospholipids are amphipathic - carry a double charge therefore the final stage of production takes place at the interface of the cytosol/membrane
Catalysed by membrane associated enzymes
Describe the 4 major stages of inserting the fatty acids into the SER?
- Two fatty acids are esterified to the phosphorylated glycerol phosphate backbone - the 2 long hydrophobic chains anchor the molecule to the membrane on the cytosolic leaflet
- To add the specific head group - a phosphatase removes phosphate group
- A polar head group (e.g. Phosphoryl choline) is transferred by cytosine diphosphocholine (CDP-choline) to the exposed hydroxyl group
- Flippases catalyse the movement of phospholipids from the cytosolic to the endoplasmic leaflet
Describe flippases?
This maintains a stable/even ER membrane synthesis on both sides of the bilayer
Not spontaneous - requires the passage of a polar head through a hydrophobic membrane (often use ATP)
How is sphingolipid synthesis different from glycerophospohlipids?
Ceramide is produced at the SER
Converted to either glycolipids orsphingomyelin in theGolgi
The precursor but not final sphingolipid is produced at the SER - they often undergo further modifications in the Golgi
