Download ch4 FA 11 - Cal State LA

The Plasma Membrane
• Functions
– Compartmentalization
• Plasma membrane, nuclear envelope, mitochondria, chloroplast,
lysosome, peroxisome, liposome
– Scaffold for biochemical activities
• Enclose compartments and are compartments themselves
– Ubiquinone dissolved in inner mitochondrial membrane
– Diacylglycerol in plasma membrane
The Plasma Membrane
• Functions
– Selective permeability barrier
• Prevent unrestricted movement of molecules
• Maintain gradients
– Transport solutes
• contains channels and pores that allow selective movement
and establish gradients
The Plasma Membrane
• Functions
– Signal transduction
• Location of receptors, some effectors, 2nd messenger precursors (PIP2)
– Cell-ECM, cell-cell interactions
• Integrins, cadherins
– Energy transduction
• Proton gradients coupled to ATP synthesis (mitochondria, chloroplast)
The Plasma Membrane
• Structure
– Outer leaflet faces extracellular space
– Inner leaflet faces cytoplasm
The Plasma Membrane
• Structure
– Lipid bilayer
• Thin sheet held together
noncovalent interactions
– Fluid mosaic model
• Lipids are in a fluid
mobile state, not static
The Plasma Membrane
• Composition
• Amphipathic
• Phospholipids
• Glycerol backbone
» Head group
» Phosphate
» Glycerol
» 2 fatty acids (C18)
• Composition
– Phosphoglycerides
– Head group types
• Choline (+ charge)
• Serine
• Ethanolamine (+ charge)
• Inositol
The Plasma Membrane
• Sphingolipids
– No glycerol backbone
– Sphingosine
– Ceramide = sphingosine +
fatty acid (amide bond)
– Sphingomyelin = choline +
phosphate + ceramide
– Glycolipids = sugar +
ceramide
• Cerebrosides and
gangliosides
• Essential in neuronal
function
• Cholesterol
– Up to 50% of animal membranes
• Absent from most plant cells and all
bacteria
• Planar ring restricts movement of lipid
tails
The Plasma Membrane
• Membrane carbohydrates
– ~ 90% attached to protein
remainder = glycolipid
– Glycosylation: attachment of sugar
to a protein
– Modification on proteins at amino
acids N, S, T
– All carbohydrates face away from
cytosol
• Plasma membrane glycoprotein
carbohydrates face outside cell
• ER glycoprotein carbohydrates
face into lumen
The Plasma Membrane
• Membrane carbohydrates
– Blood type glycolipid
• A = allele 1
• B = allele 2
• O = null
• AB = allele 1 / allele 2
heterozygote
The Plasma Membrane
• Membrane proteins
– Integral
• Receptors, channels, transporters
The Plasma Membrane
• Membrane proteins
– Peripheral
• Nuclear lamina
• Membrane skeleton
The Plasma Membrane
• Membrane proteins
– Lipid-anchored
• Outside = GPI-anchor =
Glycosyl-Phosphatidyl-Inositol
• Cytosolic = hydrocarbon
(palmitoyl) attached (e.g Ras,
G-alpha-s/i/q)
The Plasma Membrane
• Membrane fluidity
– Liquid state versus frozen crystalline state
• Either extreme is undesirable
The Plasma Membrane
• Membrane fluidity
– Transition temp, melting temp (Tm)
• Saturated vs unsaturated C-C bonds
– Saturated fatty acids pack well,
increase Tm
– Unsaturated pack less well,
decrease Tm
• Length
– Long, increase Tm
– Short, decrease Tm
The Plasma Membrane
• Membrane fluidity
– Transition temperature, melting temperature (Tm)
• Cholesterol disrupts packing but also reduces fatty acid mobility
– Broadens melting curve
– Increases membrane durability
– Decreases permeability (membrane is more hydrophobic)
The Plasma Membrane
• Movement
– Lateral diffusion within a leaflet is possible
– Flipping from one leaflet to the other is thermodynamically
unfavorable
The Plasma Membrane
• Membrane skeleton
– Required for mechanical
strength of membrane
– Disease: muscular dystrophy
• Mutations in dystrophin
– spectrin family
member in muscle
• Contraction of muscle
leads to disruption of the
outer membrane
The Plasma Membrane
• Membrane skeleton
– Spectrin alpha/beta heterodimer
• Forms a 200nm flexible,
elastic fiber
• Binds ankyrin, actin,
tropomyosin
– Ankyrin binds “Band 3”
transmembrane protein
The Plasma Membrane
• Transport
– Diffusion: [high] to [low] is spontaneous
– H2O reasonably free to diffuse
• Aquaporins allow faster movement
• Transport
– Ions and polar compounds are largely unable to penetrate lipid
bilayers
The Plasma Membrane
• Ion channels
– Ligand-gated
• allostery
– Mechano-gated
• Mechanical force on membrane (stretch, compression, etc)
– Voltage-gated
• Charge difference across membrane
– Resting state ~ -70mV
– More negative inside cell
– Selectivity
• K+
~ 0.27nm diameter
• H2O ~ 0.28nm diameter
• Na+ ~ 0.19nm diameter
• H+
< 0.1 nm diameter
– How to let K+ in without
letting Na+ in
• K+ Ion channels
• K+
~ 0.27nm diameter
• H2O ~ 0.28nm diameter
• Na+ ~ 0.19nm diameter
• H+
< 0.1 nm diameter
– Selectivity filter
• Backbone carbonyl groups
arranged to form “rings”
with a 0.30nm diameter
• Can substitute for water
hydration shell around an
ion
• Smaller ions have far less
favorable bonding
interactions with “rings”
The Plasma Membrane
• Facilitated diffusion
– Transporter catalyzes movement
from one side to other, driven by
movement down concentration
gradient
– 1st step of glycolysis lowers
cytoplasmic concentration
– Can be regulated
The Plasma Membrane
• Active transport
– Requires E input to move substances against a concentration gradient
[K+]in = 100mM
[Na+]in = 10mM
[K+]out = 5mM
[Na+]out = 150mM
– E sources, ATP hydrolysis, light, other substances moving down gradient
– Na+/K+ ATPase
• ATP hydrolysis achieves:
– 3Na+ moved out
– 2K+ moved in
» Unequal ratio (3:2) directly contributes to
net negative charge inside cell (resting potential ~ -70mV)
– Ca2+ ATPase (for ER Ca2+)
– H+/K+ ATPase secretes acid into stomach (0.16 N HCl, ~ pH 1)
The Plasma Membrane
• Active transport
– H+/K+ ATPase secretes acid into stomach (0.16 N HCl, ~ pH 1)
– Prilosec directly inhibits H+/K+ATPase (irreversible)
The Plasma Membrane
• Co-transport
– Use E in existing gradients
– Also known as “secondary
active transport”
– Na+/glucose cotransporter
• Symporter
• 2Na+ move in
• 1 glucose moves in
• Can work against a
20,000 fold gradient
– Na+/H+ antiporter
• Na+ moves in
• H+ moves out
• Regulates cytoplasmic
pH