Plasma Membrane Components

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