Week 9(L16-17): Movement across membranes, signal transduction, ECM, & mitochondria

What is the transmembrane domain (TMD)?

What is the transmembrane domain (TMD)?

• largely hydrophobic (uncharged) alpha-helical peptide sequence that spans the membrane

What does the TMD consist of?

amino acids with hydrophobic side chains

TMD permanently attaches the protein to what?

Plasma membrane

What interacts with the hydrophobic TMD?

hydrophobic fatty acid tails

The TMD can facilitate what?

protein-protein interactions

What do lipid bilayers NOT allow?

many compounds cannot pass through freely

What type of molecules can cross membranes relative easily?

small, uncharged

What are examples of small and uncharged molecules?

H2O

O2

CO2

NO

What type of compounds cannot easily cross lipid bilayers?

large

polar

charged

What are examples of large, polar, and charged compounds?

Ca+

Na+

K+

glucose

What are the 4 basic mechanisms for moving molecules across membranes?

1. simple diffusion

2. diffusion through channel

3. facilitated diffusion

4. active transport

What does passive movement of substances across cell membranes rely on?

concentration gradient

What is a concentration gradient?

molecular concentrations of substances across the membrane

Molecular concentrations move from _______ across the membrane

1. high to low

2. low to high

1. high to low

What does simply diffusion only work for?

very small and uncharged molecules (H2O, O2, CO2)

What are aquaporins?

• specific water channels

• H2O moves through in single file down the concentration gradient

Channels are formed by what?

integral membrane proteins - multiple subunits that line an aqueous pore

Channels are effective for what?

small charged molecules - ions

(Na+, K+, Ca2+, Cl-)

Ions move ______ concentration gradients

down

Channels are selective

only allow certain types of ions to pass (uniporter)

What are often gated?

ion channels

What does it mean to be gated?

can be turned on/off in response to different signals/stimuli

What are the two types of gated ion channels?

1. voltage-gated (Na+ & K+)

2. ligand-gated (neurotransmitters)

Voltage-gated channels respond to what?

changes in charge across membrane

Under non-depolarized conditions, neurons have what?

low [Na+] inside

Ligand-gated channels respond to what?

binding of specific molecule on its surface (ligand)

What does the binding of a ligand produce?

conformational change in structure of the receptor/channel

What is tetrodotoxin (TTX)?

a very potent neurotoxin; Na+ channel blocker

How does TTX work?

• inhibits firing action potentials in neurons by binding to voltage-gated sodium channels in nerve cell membranes

• blocks Na+ ion passage into the neuron

• prevents the nervous system from carrying messages to muscles

What is curare?

competitive antagonist of the nicotinic acetylcholine receptor (nAChR)

What does curare do?

• occupies same position on receptor as ACh with ≥ affinity

• elicits no response

What is an example of curare?

non-depolarizing muscle relaxant

What was curare used as?

a paralyzing poison + hunting tool

In facilitated diffusion, compounds bind to integral membrane called a

facilitative transporter

In facilitated diffusion, what allows for a compound to be released on the other side of the membrane?

a change in transporter conformation

Most animal cells import glucose from the blood into cells _____ via _______

down a concentration gradient

facilitative transporter

4 steps of importing glucose

1. transporter ready to accept glucose molecule

2. glucose accepted by the transporter

3. The intracellular side of the transporter opens

4. glucose released, cycle repeats

What is the solution to moving substances from a LOW concentration to a HIGH concentration? (against the concentration gradient)

chemical gradient of a 2nd molecule that would NOT reach extracellular/intracellular equilibrium

Symporter

both molecules are transported in the same direction

Describe the Na+ Glucose Symporter

• 2Na+ & 1 glucose bind to outward binding site of transporter

• conformation change in transporter occurs (occluded conformation)

• transporter adopts inward-facing conformation

• 2Na+ dissociate in the cytosol

• glucose gets pushed in

Antiporter

the concentration gradient of one molecule is used to transfer a 2nd molecule in OPPOSITE directions

What is an example of an antiporter?

Na+/H+ exchanger

Where is the Na+/H+ exchanger located?

in the nephron of the kidney

How does the Na+/H+ exchanger work?

• transports Na+ into the cell

• forces H+ out of the cell

• maintains pH and Na levels in specific kidney cells

Active transporter

an integral membrane protein a compound specifically binds to

What causes a change in conformation of the transporter? (active)

hydrolysis of an ATP molecule

What does the hydrolysis of an ATP molecule allow for in active transportation?

molecule is released on other side of membrane

What does active transport require?

energy input in the form of ATP

What maintains cellular [Na+] and [K+] using ATP?

the Na+/K+ ATPase

Describe the Na+/K+ pump

• 3Na+ exit cell, 2K+ enter cell

  • important to maintain higher Na+ concentration OUTSIDE than INSIDE the cell

How do cells achieve and sustain the Na+ chemical gradient for non-stop activity of Na+ glucose symporter?

spend energy (ATP)

What are two mechanisms in which molecules move across membranes?

passive

active

What are the passive mechanisms?

What are the active mechanisms?

How are TTX and curare related?

toxins that interfere with movement through ion channels

ECM components are produced and secreted by what?

cells

ECM components are assembled into what?

an extracellular network

What are the major components of the ECM?

proteins - collagen

glycoproteins - laminin, fibronectin

proteoglycans

What are proteoglycans?

proteins with a polysaccharide chain?

What are the functions of the ECM?

• cell adherence

• cell communication

• cell shape

• mechanical support

• structural integrity

• barrier

Anchor membrane proteins - integrins

interact with ECM components

what do anchor proteins assist in?

• tissue formation

• coordinated cell function

• cell communication

What is the ECM abundant in?

connective tissues (tendons, ligaments, dermis)

What cells have walls?

NON-ANIMAL

• bacteria

• plants

• fungi

Plant cell walls = ?

ECM

Plant cell walls are composed of what?

• cellulose

• hemicellulose

• pectin

• protein

Plant cell walls provide what?

structural support to cell + whole organism

Plant cell walls protect cells from what?

• mechanical damage

• pathogen attack

Membrane proteins play a major role in what?

signal transduction

• converts extracellular signal → intracellular signal(s)

Signal transduction allows cell to do what?

rapidly respond to events happening in their environment

• grow

• divide

• survive

• move

• differentiate

What are ligands?

small molecules that bind to receptor

What does ligand binding change?

conformation of receptor protein

What does the ligand not do?

enter the cell

What side of the receptor protein is affected by the conformation change?

cytosolic side

What can conformation changes activate?

other proteins in cytosol/membrane bound

What are the 3 stages to signal transduction?

1. ligand binds to receptor

2. signal transduction → 2nd messenger (cAMP, Ca, G-protein)

3. cellular response: growth, division, glucose→glycogen

What are some diseases caused by signal transduction defects?

• cancer

• diabetes

• brain disorders

Glycogenolysis

how epinephrine activates glycogen→glucose

Where is epinephrine made?

in the adrenal glands

What does epinephrine bind to?

receptor on liver cell (hepatocyte)

___________ will recruit G-protein and allow the binding of GTP to turn it on

active receptor

The yellow subunit of the G-protein dissociates and turns ON what?

Adenyl cyclase → causes accumulation of cAMP inside cells

At the end of glycogenolysis, what enzyme will release glucose units?

phosphorylase-P

Function of mitochondria

• ATP synthesis

• apoptosis

Function of chloroplast

• photosynthesis

• ATP synthesis

What is the Endosymbiotic Theory?

organelles from eukaryotic cells with two membranes represent formerly free-living prokaryotes taken on inside the other in endosymbiosis

What is the supporting evidence of the Endosymbiotic Theory

1. binary fission of mitochondria & plastids

2. circular DNA inside organelles similar to bacteria

Describe aerobic respiration

• converts in presence of oxygen energy stored in food into chemical energy stored in ATP

• by-product: CO2

Describe photosynthesis

building carbs using sun energy and CO2

What is the chemical equation for aerobic respiration?

CH2O + O2 → CO2 + H2O + ATP

What is the chemical equation for photosynthesis?

CO2 + H2O → CH2O + O2

What does the Outer mitochondrial membrane - OMM contain?

• enzymes w/diverse metabolic functions (lipid metabolism)

• porins → large channels permeable (PASSIVE) to many molecules when opened (ATP, sucrose)

What is the protein:lipid ration in the Inner mitochondrial membrane?

3:1

Cristae

• double-layered folds in the IMM

• increase membrane surface area

• contain machinery for aerobic respiration and ATP formation

What is the IMM rich in?

cardiolipin

What is cardiolipin?

• phospholipid

• characteristic of bacterial membranes

• needed for optimal function of many enzymes

The mitochondria has 2 _________

aqueous compartments

What are the 2 aqueous compartments of the mitochondria?

1. intermembrane space separates OMM + IMM

2. matrix → high protein content, gel-like space containing ribosomes and genome (DNA)

What does cellular respiration use to produce ATP?

chemical energy stored in carbs and lipids

What kind of reaction is involved in cellular respiration?

catabolic