Download Lipids: Classes and more Schemes and Mind Maps Biochemistry in PDF only on Docsity!
Lecture 28 (12/1/21)
Lipids & Membranes
A. Lipids
- Roles
- Classes a. Fatty Acids b. Fats c. Waxes d. Membrane lipids e. Terpenes B. Membranes
- Introduction
- The 4 S’s a. Size b. Solubility c. Shape d. Stability
- Models for Membrane structure a. Old Model b. Data c. Fluid Mosaic Model d. Testing the model
- The Red-Blood Cell Membrane
- Membrane Asymmetry a. transverse b. lateral c. anchoring
- Membrane Fluidity
TODAY
- Reading : Ch11; 370-
- Problems: Ch11; 5,6,8,9,12,13,
NEXT
- Reading : Ch7; 220-
- Problems: Ch7; 1,2,3,5,
Lipids: Classes
Biological molecules that are characterized by low solubility in water, that is, are relatively hydrophobic.
Classes of Lipids
- Fatty acids
- Fats (triglycerides)
- Waxes
- Membrane Lipids
- Isoprenes
2 & 3 are sometimes classified together as ”simple lipids”
They have a high hydrocarbon content
Lipids: Fatty Acids
Need to Know: Common names, structure, symbol (e.g., 18:3D9,12,15)
(D^15 )
(D9,12,15)
(D9,12)
(D^9 )
(D6,9,12) (D5,8,11,14)
(D^9 )
Classification of Membrane Lipids
Two major categories based on the structure and function:
- Lipids that contain phosphate
- Lipids that do not contain phosphate
- each can be further separated into:
- Glycerol-based and sphingosine-based
Lipids: Membrane Lipids
Sphingophospholipids Sphingoglycolipids
Sphingolipids
Cholesterol
(animals)
PS, PE, PC
sphingomyelin
Models for Membrane Structure
TESTING OLD MODEL: DATA
- & 2) Wash isolated membranes with high-salt solutions or changes in pH. Ø Removes some but not all proteins Ø This leads to an operational definition of peripheral (those that wash off with 0.5 M salt), an integral (those that remain after washing) membrane proteins
0.5 M NaCl
d & c
detergents
a, b,^ &^ e
Integral
Peripheral Amphitrophic and GPI-linked proteins
Models for Membrane Structure
Lipids: Membranes
TESTING OLD MODEL: DATA
- Isolated membrane proteins should show lots of b-structure. Ø Peripheral membrane proteins looked like cytosolic proteins Ø CD showed there was actually more a- helix than b-structure Ø Integral membrane proteins had patches of hydrophobic residues in their sequence
Models for Membrane Structure
OMG!!!
NOT smooth inside!
Oops, maybe
proteins DO span the
membrane.
TESTING OLD MODEL: DATA
- Importantly, NO PROTEINS ON THE INSIDE. Ø So, lets look: performed Freeze-fracture EM on cell membranes Ø This immediately became an explanation for Integral membrane proteins.
(1000 Å)
- Lipids form a viscous, two- dimensional solvent into which proteins are inserted and integrated more or less deeply.
- Proteins can either be embedded in or associated with the membrane:
NEW MODEL (1972)
Fluid Mosaic Model proposed by SJ Singer & GL Nicholson
Models for Membrane Structure
Lipids: Membranes
- Integral membrane proteins are firmly associated with the membrane, often spanning the bilayer.
- Peripheral membrane proteins are weakly associated and can be removed easily. o Some are non-covalently attached. o Some are linked to membrane lipids (amphitrophic)(more later). This model was also testable!
(1924-2017)
SJ Singer
Lateral Movement is fast
A Single Lipid in 56 ms
Transverse Movement is
SLOW
Spontaneous flips from one leaflet to another are rare because the charged head group must transverse the hydrophobic tail region of the membrane.
Testing Fluid Mosaic Model of Membrane Structure:
FRAP
2
Lipids: Membranes
The Fluid Mosaic Model: Details
Introduction
The 4 S’s
Size Solubility Shape Stability
Models for Membrane structure
Old Model Data Fluid Mosaic Model Testing the model
The Red-Blood Cell Membrane
Membrane Asymmetry
Lipids transverse lateral Protein anchoring glycoproteins
Membrane Fluidity
Lipids: Membranes
The Structure of the Red-blood Cell Membrane
Lets look closer are one of these integral membrane proteins, glycophorin.
Asymmetry
- Membranes are very asymmetric.
- All kinds of asymmetry: Components–lipids, proteins Types–transverse, lateral
– Lipids (transverse):
- Two leaflets have different lipid compositions.
- The outer leaflet is often more positively charged.
- If Phosphatidylserine is found outside, it has a special meaning:
- platelets: activates blood clotting
- other cells: marks the cell for destruction
How is this asymmetry maintained?
Rat liver plasma membrane
Net Charge: 0 0
– Lipids (transverse): Flippases
transverse diffusion.
- Though often referred to by category name “flippase,” there are unique unidirectional and bidirectional enzymes to catalyze lipid movement.
- Some flippases use energy of
ATP to move lipids against the
concentration gradient.
Lipids: Membranes
There exits lateral asymmetry ; these enzymes determine and
Asymmetry
Asymmetry
Lipids (lateral):
1) On the inner leaflet, can induce
phosphoserine to coalesce with calcium.
2) On the outerleaflet, can induce
“raft” formation; the coalescence of
particular membrane lipids (cholesterol,
sphingoglycolipids, sphingomyelin, etc.)
Lipid distribution in a single leaflet is not random or uniform.
Asymmetry
Lipids: Membranes
Lipids (lateral): Membrane Rafts
Lipid rafts:
- contain clusters of sphingoglycolipids with longer-than-usual tails and cholesterol
- are more ordered (not as fluid)
- contain specific doubly or triply acylated proteins
- allow segregation of proteins in the membrane
Proteins:
1) anchored
2) glycoproteins
Asymmetry
Ø Some membrane proteins are lipoproteins containing a covalently linked lipid molecule. Ø The lipid part inserts into the membrane. Ø The protein is then anchored to the membrane. Ø These are the aforementioned “Amphitropic” membrane proteins
- This allows targeting of proteins to the membrane, either internally (FA or isoprenes), or externally (GPI- linked).
- Some, such as GPI anchors are found only on the outer face of plasma membrane.
- This is a reversible process.
Asymmetry
Lipids: Membranes
Proteins:
1) anchored
2) glycoproteins
Found ONLY ever on the OUTSIDE of Cells
Introduction
The 4 S’s
Size Solubility Shape Stability
Models for Membrane structure
Old Model Data Fluid Mosaic Model Testing the model
The Red-Blood Cell Membrane
Membrane Asymmetry
Lipids transverse lateral Protein anchoring glycoproteins
Membrane Fluidity
- Cells must maintain fluidity for membranes to function properly.
- Depending on their composition and the temperature, the lipid bilayer must maintain a fluid phase; if cooled, it undergoes a phase transition and goes to a gel state. - liquid-ordered state (i.e., “gel phase”): individual molecules do not move around – NOT ACTIVE - liquid-disordered (or liquid crystal) state (i.e., “fluid phase”): individual molecules can move around – ACTIVE
NOT ACTIVE ACTIVE Semi-solid Fluid
Cooling
Fluidity
Lipids: Membranes
Membrane Phase Transition
ACTIVE
NOT ACTIVE
- Due to its small polar head, it lies deeper in the bilayer than the phospholipids
- Cell membranes of many eukaryotes contain sterols. - cholesterol in animals - phytosterols in plants - ergosterol in fungi
- Cell membranes of aerobic prokaryotes contain hopanols.
H O
cholesterol
Cholesterol Increases Membrane Rigidity and Permeability
Fluidity
Membrane Phase Transition
Fluidity
Lipids: Membranes
Organisms Can Adjust the Temperature of the Phase
Transition by Changing the Membrane Composition
- Membrane fluidity is determined mainly by the fatty acid
composition and melting point.
- The temperature of the phase transition (T (^) m ):
- Melting temperature higher with more saturated fatty acids.
- Melting temperature higher with longer fatty acids.
- Melting temperature lower with more unsaturated fatty acids.
- Melting temperature lower with shorter fatty acids.
- Therefore, at higher temperatures, cells need more long,
saturated fatty acids.
- And at lower temperatures, cells need more shorter,
unsaturated fatty acids.
TABLE 11-2 Fatty Acid Composition of^ E. coli^ Cells Cultured at Different Temperatures Percentage of total fatty acids a 10 ˚C 20 ˚C 30 ˚C 40 ˚C
Myristic acid 4 4 4 8 Palmitic acid 18 25 29 48 Palmitoleic acid 26 24 23 9
Oleic acid 38 34 30 12
Hydroxymyristic acid 13 10 10 8 Ratio of unsaturated to saturated b^ 2.9 2.0 1.6 0. SOURCE: Data from A. G. Marr and J. L. Ingraham, J. Bacteriol. 84:1260, 1962. a (^) The exact fatty acid composition depends not only on growth temperature but on growth stage and growth medium composition. b (^) Ratios calculated as the total percentage of 16:1 plus 18:1 divided by the total percentage of 14:0 plus 16:0. Hydroxymyristic acid was omitted from this calculation.
Fluidity
