Lecture 4
Plasma Membrane Components
phospholipid bilayer
phospholipids (major)
glycolipids (lipids attached to sugar)
sterols (such as cholesterol)
lipids
proteins
etc…
Fluid Mosaic Model
all components can around within their layer
Phospholipids
amphipathic molecules (polar end, non-polar end)
Polar Head
polar head group
phosphate group
Glycerol Backbone “glycerophospholipid”
NonPolar Tails
fatty acid side chains
one saturated
one unsaturated
Sphingomyelin structure
phospholipid
Polar Head Group : choline
Backbone: Sphingosine
Phosphatidyl-
phospholipids of the membrane head groups
Ethanolamine
Serine
Choline
Glycolipid function
in membrane
cell cell signaling
cell cell recognition
membrane stability
ex:glycosphinolipid
Sterols
in membrane
ring ring structures
Cholesterol
type of sterol
maintains membrane integrity
prevent phospholipids from packing together too tightly
Ceramide function
structural support
signaling
apoptosis
Ganglioside function
signal transduction
synaptic transduction
amphipathic phospholipids
ASMD (ASM deficiency)
Niemann-Pick Disease
a disease that involves and abnormality in sphingomyelin breakdown
an enzyme that breaks down sphingomyelin in acidic conditions
specifically the lysosome
Acid Sphingomyelin (ASM)
Symptoms of ASMD
enlarged liver, spleen
difficulty eating
loss of muscle tone
lung disease and eye problems
low platelet count
delayed growth
Treatment for ASMD
drug used as replacement therapy for ASM
recombinant human acid sphingomyelinase
Alpha Helix (interaction with membrane)
single pass
Multiple Alpha Helices (interaction with membrane)
multiple pass
A beta barrel
rolled up beta sheet
GPI Anchor
attached to membrane via oligosaccharide linker to phosphatidylinositol
“Lipid rich coat” on membrane function
facilitate interactions with extracellular matrix
protect cell from mechanical and chemical damage
keep different cells at a distance
What is the function of acid sphingamyelinase?
facilitates the synthesis of sphingamyelin
involved in the break down of ^
involved in the breakdown of ceramides
involved in the associated disease
involved in the break down of sphingamyelin
What is the function of the glycocolyx?
Transporter
usually specific
bind solute
undergo conformational change to expose the solute to the other side
Channels
sometimes specific
opened by conformation change and form pores across bilayer
usually faster than transporters
common transport mechanism for drugs
passive
occurs via coupled transport
secondary active transport
Concentration gradient
for uncharged molecules
the difference in the concentration of the molecules on the two sides of the membrane if the conc. gradient
Electrochemical Gradient
charged molecules
the concentration and the electrical gradient combined
net charge difference across the membrane
Drugs that can pass through the membrane via diffusion
NSAIDs
ibuprofen
aleve (naproxen)
aspirin
Ethanol
Simple Diffusion
small uncharged molecules
lipids
gases
down conc. gradient
No E
pacssive
Facilitated Diffusion
via channels and transporters
down conc. gradient
No E
passive
In what types of cells would you see an abundant amount of aquaporins?
cells that must transport water at a high rate
epithelial
kidney
Ion Channels
transport ions
selective
passage occurs in single file starting at the narrowest part of the channel which is the selectivity filter
esp. important in neurons
Gated Channels
(lots of ion channels)
open briefly in response to stimulus then close again
Calcium Channel
type of ion channel
found in:
muscle cells (contraction)
neurons (neurotransmitter release)
endocrine cells (triggers release)
immune cells (can regulate immune responses)
Calcium Channel Blockers
(what is it used to treat)
block low of calcium ions
muscle relation and dilation
treats: high BP, angina (not enough O2 for heart), heart rhythm disorders
How is an AP triggered in a neuron?
change in electrical charge cause by movement of ions across membranes through ion channels
P - Type Pump
(+examples)
ATP driven pump
phosphorylate themselves during the pumping cycle
ex. sodium potassium pump
calcium pump
ABC transporters
atp driven pump
pump small organic molecules
Functions of the electrochemical gradient
transport
electrical signaling
maintenance of cell volume (regulate movement of water)
maintenance of membrane potential (difference in electrical charge across membrane)
Digoxin
used to treat heart conditions
HF
inhibits Na+/K+ (disrupts)
disrupts Na+/Ca2+ exchanger
normally pumps Ca2+ out of cell
increased [Ca2+]
beneficial :improves contraction and controls certain types of irregular heart beats
Ca 2+ transporter
establishes ca gradient into the cytoplasm
activated cellular pathways
two types:
P Type Ca2+ ATPase
Na+/Ca2+ exchanger (antiporter), driven by the Na+ gradient
see digoxin
P Type Ca2+ Pump
ATP Driven
high levels in the sarcoplasmic reticulum (SR) membrane of skeletal muscles
pumps ca2+ in SR
Ca2+ transporter in SR/ER mechanism
ATP bound pump: opening only accessible to the cytosol side of ER
conformational change hydrolyzes ATP → leaves ADP
ADP replaced by ATP
releases Ca2+ into ER/SR
H goes into pump and is released into cytosol
ABC Transporters
largest family of ATP transport domains
two transmembrane domains that form a channel
two ATP domains on cytoplasmic side
ATP binding cassettes
ABC Transporter Mechanism
substrate binds to binding site
ATP binds to binding cassettes
the two cassettes come together
ATP is hydrolyzed into ADP and Pi
provides E
Transporter undergoes conformational changed solute is transported
MDR
multidrug resistance protein
aka P-glycoprotein (Pgp)
ABC transporter
elevated in many human cancer cells
problem in cancer treatment: cells resistant to drugs (pumps it out of cell)
treatment targets cancer cells that lead to selection of cells that overproduce MDR
Cancer Cell treatment options that are used in an attempt to avoid MDR
Combination therapies (mult. drugs)
Drug Sequencing (deliver drugs in specific order)
Drugs that have inhibitory affect on MDR transporters
Nanotechnology (special delivery)
Chloroquine
antimalarial drug
P. Falciparum
invades blood cells
causes malaria
CTFR
cystic fibrosis transmembrane conductance regulator protein
atypical ABC
functions more like a channel than a carrier
Cl- transporter
Cystic Fibrosis
(+ treatment)
mutation in CTFR gene
treatment: some drugs potentate CTFR function
Kalydeco (ivacaftor)
(how it works)
binds to mutant CTFR
increases its ability to open
facilitates Cl- flow
Sodium Glucose Co-Transporter (SGLT)
coupled, symporter
glucose transport
utilizes E from Na+/K+ (electrochemical gradient)
intestinal and kidney cells
NOT GLUT1 transporter!
Serotonin Transporter (SERT)
(type, aka, lo, function)
coupled
aka reuptake transporter
serotonin from synaptic cleft
Na+ dependent (concentration gradient)
terminates the signal between the two neurons
Serotonin Reuptake Inhibitors (SSRIs)
(function and how it treats)
block SERTs
inhibits reuptake of serotonin at synaptic clecft
increases serotonin in cleft
treats: depression, anxiety
Prozac and Zoloft
SSRIs
treatment for depression and anxiety
Transporters found on GUT epithelial cells
Na+ linked symporters at atypical (absorptive/outside)
transport nutrients into the cell
Uniporters — basolateral (inside)
allow nutrients to leave
down conc. gradient and enter bld stream