• Integral: transmembrane proteins that span both sides. Have charged or polar amino acids on the outside that can react with water. Have alpha helix that spans the bilayer.
• Peripheral: they are attached to just one side of the bilayer; they attach through interactions with polar/charged head groups and other proteins

1. Phospholipids: what makes up the bilayer
2. Sphingolipids: these are more rigid and can help protect the srtucure. Glycolipids also help with this.
3. Cholesterol: this also helps control bilayer rigidity; they also allow H2O permeability. Osmosis is influenced by the amount of cholesterol present in the bilayer.

Different lipids can effect membrane thickness and curvature.

They are clusters of certain types of proteins and lipids on the plasma membrane. Their close proximity and help favor or control certain protein-protein interactions.

Some proteins like to be in rafts while some do not.

1. The types of lipids that make up the bilayer
2. Whether or not the fatty acid tails are saturated or unsaturated.

Active Transport

Why do we need it?

This is a mode of transporation across the membrane that USES energy. This is because active transport moves ions/molecules AGAINST their concentration gradient (from low to high).

We spend energy with these because cells cannot reach equilibrium. It means death!

1. ATP Powered Pumps (active transport)
2. Ion Channels (passive transport)
3. Transporters (eihter)

Ion Channel

What are the three types?

Ion channels are selective pores that span across the membrane, allow ions to flow through. However, they are gated.

1. Voltage-gated: opened by a change in membrane potential (e.g. neurons)
2. Ligand-gated: binding of chemical ligand opens them (often called receptors)
3. Stretch activated: change in membrane tension opens them

Unlike an ion channel which opens and lets ions flow freely through until it closes, a uniporter carries one molecule at a time.

The molecule enters a shape specific opening and the protein closes on one side and opens on the other, releasing the molecule.

This process is facilitated diffusion.

Transporters can only transport molecules at a certain rate. Transport rate may start off at a very quick pace, but when the outside concentration of a molecule reaches a certain point, transport rate will slow down.

Saturation is caused because there is only a finite number of transporters on the membrane.

These pumps use ATP hydrolysis (ATP --> ADP) for energy that is used to transfer molecules against their gradient/maintain the gradient.

Na and/or K bind to protein. ATP binds to protein and the breaking of a phosphate bond releases energy, giving the protein the energy to change conformation and push a molecule through the bilayer against its gradient. (Na in and K out).

A cotranspoter is an ion channel that can move two different ions at once. It is called secondary active transport. One molecule moves down its concentration gradient while (passive). The movement of this molecule gives the pump the power it needs to move the other molecule against its gradient. This is called the waterfall effect.

1. Antiporters: the two ions move opposite directions
2. Symporters: the two ions move the same direction

THE INSIDE IS NEGATIVE RELATIVE TO THE OUTSIDE

On the inside of the cell, 3 Na ions enter the pump and ATP binds. Hydrolysis releases energy causing a conformational change, pumping the sodium out. 2 K binds and a conformational change (waterfall effect) moves them in. Since only 3 positive charges go out and 2 positive charges go in, there is a negative charge on the inside.

They are electrically excitable.

1. Muscle
2. Nerve
3. Endocrine

1. Neurotransmitters from the previous nerve bind to ligand-gated channels to allow the flow of sodium in.
2. This change in charge activates the voltage-gated channel in the local area, opening them, letting more sodium in. This depolarized wave/action potential procedes down the nerve.
3. At the end of the nerve, voltage gated calcium channels open allowing calcium to bind to vesicles, release neurotransmitters to the next cell.

1. Na and K ATPase pumps are unregulated and always working to maintain and reset the gradients and charge separation. This is not enought by itself.
2. The voltage gated sodium channels will automatically close after a period of time.
3. Potassium voltage channels open as a result from the same charge that opens the Na channels, helping to reset the charge separation. However, they take longer to open, so it gives the neuron enough time to actually fire the signal.

What are enzymes and their characteristics?

Give an example.

Enzymes are catalysts. They change the rate of a reaction without being consumed! They do not supply energy or change an unfavorable reaction to favorable. They do speed up an energetically favorable reaction.

They reduce the the amount of free energy that is needed for a reaction to occur.

Glucose + ATP --> Glucose 6-phosphate + ADP is sped up when an enzyme is added.

1. "Lock-and-Key": this increases the probability that two proteins will bump into each other by grabbing one and then grabbing the other.
2. Change substrate reactivity: can get protein out of solution in and into a different chemical environment.
3. "Induced Fit": can increase reactivity by physically bending the molecule and bonds.

• Competitive: when the inihibitor competes with the substrate for binding on the active site.
• Uncompetitive: when the inhibitor binds at a different location than the active site (allosteric).

1. Endocrine: long distance; hormones are released into the bloodstream and travel to a certain area, activating cells.
2. Paracrine: localized signaling; cell releasing molecules which bind to a second cell (e.g. synaptic transmission)
3. Contact-Dependent: literal contact

1. Extracellular signal (ligand) binds to a specific receptor on the cell membrane.
2. This triggers an intracellular signal (usually a cascade) that involves the release of a second messenger.
3. This cascade eventually ends in a physical cell response.

Just about anything a cell does can be regulated via this process.

1. Ion Coupled Receptors (ligand-gated ion channels)
2. Enzyme-coupled Receptors: signal molecule comes in form of a dimer and forms to surface receptor, causing a conformational change on the inside, which then causes an allosteric reaction.
3. G-protein coupled receptors: ligand + receptor complex leads to release/increase of 2nd messenger within the cell. When ligand binds to receptor, it activates the transducer. Transducer binds to effector, which catalyzes synthesis of second messenger.

• Calcium: causes conformational change by bending alpha helix
• Cyclic AMP
• Cyclic GMP

They are small, hydrophilic and free to diffuse.

Adenylyl cyclase is the effector. It catalyzes the production of cAMP from ATP when activated by the transducer. cAMP is the 2nd messenger.

The transducer is an allosteric activator. cAMP then acts as an allosteric activator for another enzyme.

Protein Kinase A (PKA). PKA consists of 4 subunits...

1. 2-R subunits (regulatory): they bind two cAMP each.
2. 2-C subunits (catalytic)

When cAMP binds to the R subunits, it frees up the C subunits, which are their own active protein kinases when freed.

An enzyme that transfers a phosphate from ATP to a protein. This can either turn it on OR off.

After this, a protein is considered phosphorylated.

An enzyme that removes a phosphate from a protein. This acts as a molecular switch mechanism.

Removal of phosphate does not necessarily mean the protein is turned off. It just causes a conformational change, which can change function in any way.

• Allows more regulation
• Increases amplification
• One primary signal can lead to several coordinated signals (e.g. epinephrine can active activate glycogen phosphorylase AND inhibit glycogen synthase)
• Two primary signals can lead to the same response (epinephrine and glucagon)

• Everything gets reserved! Phosphotase will come in and remove phosphate from all kinases, turning everything off, which stops cell response.
• The transducer shuts off, stopping the sythesis of the 2nd messenger.
• An enzyme comes in and degrades all 2nd messengers.

3 heterotrimeric protein subunits...

1. Beta and gamma, which don't leave each other!
2. Alpha subunit which binds GTP/GDP and hydrolysizes GTP to GDP.

• When alpha is bound to GDP, it is inactive and binds/is bound to beta-gamma.
• When alpha is bound to GTP, it is active and dissociates from beta-gamma.