Membrane Biosynthesis Flashcards Preview

Biological Membranes and Signalling > Membrane Biosynthesis > Flashcards

Flashcards in Membrane Biosynthesis Deck (15)
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1
Q

The basis of synthesis

are they made from scratch? where is the process occurring?

A

Not synthesised from scratch!

  • Produced by the expansion of existing membranes:
    1) early steps in cytoplasm producing water soluble intermediates
    2) final steps through enzymes bound to pre-existing membranes (products incorporated as they’re generated)
2
Q

Upon formation, membrane lipids must be:

A

1) Delivered to the correct leaflet of bilayer
2) Distributed to membranes of organelles
3) Distributed to the plasma membrane

3
Q

Smooth Endoplasmic Reticulum (SEM) in membrane synthesis

A

Primary site of membrane synthesis:

  • produces cholesterol and membrane phospholipids using embedded enzymes in its membrane
  • transports newly produced lipids to cellular destinations (as part of a vesicle)
4
Q

Saturated vs Unsaturated fatty acids

A

Saturated:

  • Single carbon bonds
  • Fit closer together, more tightly packed
  • Higher melting points (solid at RT)

Unsaturated:

  • Double carbon bonds - gives 30 degree kinks to chain
  • Less closely packed due to kinks
  • Lower melting point (liquid at RT)
5
Q

Cis and Trans fatty acids (unsaturated)

A

Cis

  • most common
  • 2 H atoms on same side of C=C bond hence kink forms

Trans
- H atoms on opposite sides of C=C bond (no kink)

6
Q

Fatty Acid Synthesis

Acetyl-CoA –> Fatty Acid

A

1) Pyruvate from glycolysis is decarboxylated to Acetyl CoA
2) Carboxylation of Acetyl-CoA to Malonyl-CoA (irreversible, requires 1x ATP)
3) Malonyl-CoA becomes Palmitate, catalysed by Fatty Acid Synthase (FAS): 2 Carbons provided to fatty acid (Palmitate = C16:0 saturated)
4) Palmitate = Fatty Acid precursor: lengthened to form stearate (C18:0) or longer saturated FAs
- FA elongation occurs in SEM or mitochondria

7
Q

Producing UNsaturated fatty acids

A

Fatty Acid Synthesis pathway always produces saturated FAs (Palmitate = Saturated!)

  • Desaturase enzymes are required to remove 2 H atoms from a FA allowing a C=C bond to form
  • e.g. Oleoyl-CoA formed from Stearol-CoA losing 2x H atoms
8
Q

Incorporating FAs into phospholipids in the SER membrane

A

1) 2x FAs esterified to phosphorylated glycerol backbone (Phosphatidic acid)
2) Phosphatase converts phosphatidic acid into diacylglycerol (glyceride made of 2 FAs covalently bonded (ester bonds) to a glycerol)
3) A polar group (e.g. phosporylcholine) is transferred from Cytosine DiPhosphocholine (CDP-choline) onto the exposed hydroxyl group to form a phospholipid
4) Flippases catalyse the integration of the phospholipids into the cytoplasmic leaflet

9
Q

Sphingolipid Synthesis

A

Ceramide (precursor) produced in SER

- converted into glycolipids or sphingomyelin in Golgi

10
Q

Cholesterol Synthesis in Cytosol/ER membrane

A

1) Cytosol: conversion of Acetly-CoA to HMG-CoA by HMG-CoA synthase
2) ER membrane: HMG-CoA reductase (integral membrane protein) converts HMG-CoA into Mevalonate
3) Mevalonate converted into IPP (5C)
4) 6x IPPs condense to yield Squalene (6x5=30C)
5) Squalene cyclizes: the tetracyclic product is converted into Cholesterol by membrane-bound ER enzymes

11
Q

HMG-CoA reductase

A

ER membrane integral protein: 8 transmembrane helices with a cytosolic water soluble catalytic domain

  • 5/8 TMDs compose sterol-sensing domain (cholesterol binds to switch off cholesterol synthesis, negative feedback)
  • Insig 1/2 bind to induce HMG-CoA reductase degradation (ubiquitination pathway) thus preventing mevalonate and therefore cholesterol production

DRUG TARGET:
- Statins inhibit it, reducing Low Density Lipoprotein (LDL) levels thus promoting increased LDL uptake

12
Q

Transporting Lipids from SER

A

Vesicular Transport

Transfer mediated by small, soluble lipid-binding proteins

Direct contact between membranes (mediated by membrane embedded proteins)

13
Q

Vesicular transport of Lipids from SER

A

Membrane vesicle buds off SER and fuse with other membranes

- can be selective integration, giving different organelle membrane compositions

14
Q

Lipid transfer from SER mediated by small, soluble lipid-binding proteins

A

Cytosolic, water soluble proteins that move lipids from the ER to other membranes

  • can only carry one lipid at a time
  • Only dissociates from membrane when carrying a lipid (no net transfer can occur between membranes, one in one out)
15
Q

Different lipid composition across different cellular membranes due to different sites of synthesis

A

An organelle-produced membrane is different to an imported one (different properties)

  • e.g. Cardiolipin (CL) is important in mitochondrial inner membrane so is only made there by mitochondria - CL important for cristae structure/curvature to maximise SA whilst anchoring highly cationic Cyt c