General Biochemistry II MOLB46105610 - PowerPoint PPT Presentation

Loading...

PPT – General Biochemistry II MOLB46105610 PowerPoint presentation | free to view - id: 7c3ea-ZDc1Z



Loading


The Adobe Flash plugin is needed to view this content

Get the plugin now

View by Category
About This Presentation
Title:

General Biochemistry II MOLB46105610

Description:

General Biochemistry II. MOLB4610/5610. Lecture 10. Biosynthesis of membrane phospholipids ... More unsaturated fatty acids (PE and PS often have higher amounts of ... – PowerPoint PPT presentation

Number of Views:95
Avg rating:3.0/5.0
Slides: 21
Provided by: theodorh
Category:

less

Write a Comment
User Comments (0)
Transcript and Presenter's Notes

Title: General Biochemistry II MOLB46105610


1
General Biochemistry IIMOLB4610/5610
  • Lecture 10
  • Biosynthesis of membrane phospholipids

Lehninger Ch. 21 pg. 791 - 799
2
Todays lecture
  • Membrane behavior
  • Distribution of phospholipids
  • Phospholipid synthesis in bacteria
  • Phospholipid synthesis in eukaryotes
  • Plasmalogen synthesis
  • Lipid trafficking

3
Membrane phospholipids
  • PS Phosphatidylserine
  • PE Phosphatidylethanolamine
  • PC Phosphatidylcholine ( lecithin)
  • PG Phosphatidylglycerol
  • PI Phosphatidylinositol
  • DPG Diphosphatidylglycerol (Cardiolipin)

4
Why are there so many different phospholipids ?
  • Membranes contain mainly proteins and lipids
  • Phospholipid composition dictates membrane
    behavior
  • Membranes requiring movement within membrane
  • More unsaturated fatty acids (PE and PS often
    have higher amounts of polyunsaturated fatty
    acids)
  • Lower packing densities (kinks decrease
    density)
  • Shorter fatty acid tails - fewer hydrophobic
    interactions
  • Higher membrane fluidity
  • Cell compartment specific membrane composition
  • cardiolipin found exclusively at the inner
    mitochondrial membrane - decreased leakage

5
Distribution of membrane lipids
  • Animals
  • major components are PE, PS, PC ( lecithin),
    cholesterol
  • cell membranes of the central nervous system
    contain additional lipids such as sphingomyelin,
    myelin, cerebrosides, gangliosides
  • Plants
  • PE and PC predominate
  • PI and PG are present as well
  • cholesterol is absent but replaced by
    phytosterols
  • Bacteria
  • major components are PE and PG
  • PC is rarely present, sterols are absent

6
Phospholipid synthesis in E. coli
pyrophosphate linkage
Phosphatidate
  • Requires an activated component
  • Both phosphate groups in PPi come from CTP
  • CDP-diacylglycerol can be converted to
  • Phosphatidylserine (PS) and subsequently to PE
  • Phosphatidylglycerol-3-phosphate (PG)

7
Synthesis of phosphatidylserine (PS)
phosphatidyl- ethanolamine (PE)
  • 1) Phosphatidylserine synthase reaction
  • 2) Phosphatidylserine decarboxylase reaction

CMP
PS synthase
CO2
PS decarboxylase
Phosphatidylserine Phosphatidylethanolamine
H
Lehninger pg. 793
8
Synthesis of phosphatidylglycerol (PG)
  • 1) Phosphatidylglycerol 3-phosphate synthase
  • 2) Phosphatidylglycerol 3-P phosphatase

CMP
PG-3-P synthase
CDP-diacyglycerol glycerol-3-P Phosphatidylglyc
erol-3-P
PG-3P phosphatase
Pi
Phosphatidylglycerol-3-P Phosphatidylglycerol
H2O
9
Synthesis of cardiolipin
  • Cardiolipin synthase reaction
  • (Bacteria vs. eukaryotes)

BACTERIA 2 PGs glycerol cardiolipin
EUCARYOTES CDP-diacyglycerol PG CMP
cardiolipin Phosphatidylglycerol is made
exactly as in bacteria
10
Eucaryotic synthesis of phosphatidylinositol (PI)
  • EUCARYOTES
  • CDP-diacylglycerol inositol
  • CMP Phosphatidylinositol
  • PI and phosphorylated PI derivatives
  • play an important role in signal transduction

PI kinase
11
Eucaryotic PS synthesis
PS
IN YEAST
A
PE
  • In yeast PS is synthesized like in bacteria from
    CDP-diacylglycerol
  • In mammals PS is NOT derived CDP-diacylglycerol !
    Instead it is derived from PE via a displacement
    of headgroups (Serine - ethanolamine)
  • Q Where does PE come from in mammals?

A
12
PE synthesis Mammals vs. Bacteria
MAMMALS
EUCARYOTES BACTERIA
CO2
PS decarboxylase
Phosphatidylserine Phosphatidylethanolamine
13
PC synthesis in yeast
  • The amino group of the phosphoglyceride is
    methylated 3 times using S-adenosyl-methionine as
    the methyl donor.

PE
This reaction also takes place in bacteria
(Stryer pg 718) and in the liver of mammalian
cells. Although yeast is a eucaryote it shares
share several reactions with bacteria.
14
PC synthesis in mammals
  • 1) Choline kinase mediated phosphorylation of
    choline
  • Activation of phosphocholine by CTP via CTP
    -choline cytidylyl transferase
  • Replacement of CMP by diacyglycerol resulting in
    PC.
  • This mechanism used in most mammalian cells.

15
Plasmalogen
  • Ether lipid
  • Ether R1-O-R2
  • Ether-linked alkene CH2-O-CHCH-(CH2)n-CH3
  • 1/2 of heart phospholipids
  • produced mainly in peroxisomes
  • Other ether lipids (platelet-activating factor)

16
Plasmalogen synthesis
  • Step-by-step summary of reactions
  • backbone DHAP
  • Acylation of C1 in DHAP by fatty acyl CoA
  • Exchange of an alcohol saturated fatty alcohol
    for the carboxylic group at C1
  • Reduction by NADPH
  • Acylation by a second acyl CoA at C2
  • Headgroup (ethanolamine) attachment at C3
  • Oxidation to alkene via mixed function oxidase

17
Plasmalogen synthesis
18
Platelet activating factor (PAF)
  • Ether lipid
  • Acetyl group at C2 of DHAP backbone instead of
    fatty acid
  • Synthesis similar to plasmalogen
  • from DHAP backbone
  • subnanomolar concentration of PAF
  • induce aggregation of blood platelets
  • induce muscle contractions
  • activate the immune system
  • also the mediator of anaphylactic shocks

19
Sphingolipid synthesis
  • Four stages
  • Synthesis of sphinganine
  • Requires palmitoyl-CoA serine (backbone)
  • Reduction of keto group with NADPH
  • Attachment of a fatty acid to form
    N-acylsphinganine
  • Desaturation of sphinganine to yield
    N-acylsphingosine
  • Attachment of the headgroup to produce a
    sphingolipid
  • Cerebroside (head group e.g. Glucose)
  • Glycosidic linkage instead of phosphodiester
    bonds
  • Sphingomyelin (head group e.g. choline)

20
Lipid trafficking
  • Lipids that are synthesized at smooth ER need to
    relocate to target organelle
  • Free diffusion is unlikely due to hydrophobic
    nature of lipids
  • Specific transport to target compartments
  • Requires vesicles that bud from the Golgi complex
About PowerShow.com