ZIMA Lecture 1 (Membrane Structure/Function)

Question 1

Define cell compartmentalization

Cell membranes and membranes of organelles constitute ___________\_for diffusion, preventing the mixing of distinct enviornments.

Transmembrane proteins act as a _______ of external signal or as ion channels and pumps

Answer 1

Cell compartmentalization: distinct chemical enviornments in the cytoplasm and inside intracellular organells

Cell membranes and membranes of organelles constitute an effecient barrier for diffusion, preventing the mixing of distinct enviornments.

Transmembrane proteins act as a sensor of external signal or as ion channels and pumps

Question 2

What are the three major classes of membrane lipids?

What is the most abundant type of phosholipid?

What are they composed of?

Answer 2

Three major classes of membrane lipids:
phospholipids, cholesterols, and glycolipids

Most abundant phospholipids are phosphoglycerides

Made up of: polar molecule (choline, serine, etc) - phosphate - glycerol - two fatty acid chains (one is nonsaturated)

Question 3

Which one has a kink? Nonsaturated or saturated?

Answer 3

NONSATURATED has a cis double bond that creates a kink in the fatty acid chain

Question 4

What is spingomyelin?

Answer 4

It is a phospholipid.

It forms from choline, phosphate group, sphingosine, and fatty acid chains (fully saturated)

NO CIS DOUBLE BOUNDS FOUND IN THESE FATTY ACIDS

Question 5

Explain the makeup of cholesterol.

What is its function?

Answer 5

Cholesterol:

• Sterol
• Up to one cholesterol for every phospholipid
• It contains a ring structure with polar group and a short non polar hydrocarbon chain
• Cholesterol enhances the permeability barrier of the lipid bilayer
• “It plays important surface membrane functions, it makes the membrane less permeable to water”

Question 6

What molecules are major components of eukaryotic bio membranes?

Answer 6

PHOSPHOLIPIDS (“phospholipid bilayer”)

Question 7

_________ of the phospholipid molecules causes them to form bilayer spontaneously without the use of biochemical energy.

Self-aggregation is ________ (to hide fatty chain and expose hydrophilic heads to water).

As a result the membrane possess a _______.

Answer 7

Amphiphilic nature of the phospholipid moecules causes them to form bilayer spontaneously without use of biochemical energy.

Self aggregation is energetically favorable (to hide fatty chain and expose hydrophilic heads to water)

As a result a membrane possess a self healing property.

Question 8

Which of the following is a significant factor that governs stability to biological membranes?

Answer 8

Intermolecular interaction between fatty acid chains

Question 9

Explain how lipid bilayers are a 2D fluid

Answer 9

Phospholipids in a membrane can move in different directions: rapid radial rotation, rapid lateral diffusion, slow flip flop exchange.

Flip flop RARELY occurs in eukaryotes

Phospholipid translocators catalyze the rapid flip flop of phospholipids from one monolayer to another.

Question 10

1. What does fluidity depend on?
2. What is the phase transition temp/freezing point?
3. What kind of acid chains are harder to freeze?
4. What’s the relationship between fluidity and transition temp?
5. What does cholesterol do?

Answer 10

1. Fluidity (increased membrane dynamics) depends on the membrane composition and temperature.
2. Temperature at which a lipid bilayer changes from a liquid to a crystalline state is called a phase transistion temp (or freezing point)
3. Shorter fatty acid chains or fatty acid with double bonds favor fluidity (harder to freeze)
4. As fluidity increases, the transition temperature decreases.
5. Cholesterol decreases the permeability of the lipid bilayer, but not the fluidity.

Question 11

Rafts: higher density of ________ & ________ in the lipid membrane.

Rafts could help_______

Answer 11

Rafts: higher density of sphingolipids & cholesterol in the lipid membrane. However, membrane proteins prefer specific membrane patches with whom they can interact.

Rafts could help organize membrane proteins- concentrating them for specific function (e.g. caveolae in the cell signaling)

Question 12

Monolayers in membranes are _______.

Answer 12

Because spontaneous phospholipid flip-flop is a rare event, monolayers in membranes are asymmetric.

Question 13

Lipid asymmetry of membranes plays a role in __________.

Answer 13

Lipid assymetry of membranes plays a role in converting extracellular signal into an intracellular one.

Question 14

What is the major player in cell signaling within the membrane?

What happens with apoptosis?

Answer 14

Phosphatidylinositol (located in the inner monolayer) plays an important role in cell signaling.

Apoptosis: (programmed cell death): PS translocates to the outer monolayer by unspecific translocases (“scramblase”) and by the lack of activity of PS-translocase. The presence of PS in the outer monolayers triggers the cell’s phagocytosis by macrophages.

Question 15

What is a glycolipid?

Where are they located?

Answer 15

Glycolipid: sugar containing lipids; they are made from sugars - sphingosine- fatty acids (no phosphate group)

They are located in the extracellular side of the bilayer

Question 16

What is the physiological significance of glycolipids?

Answer 16

Glycolipids protect the membrane (charged gangliosides enhance concentration of Ca 2+ near the surgace of the membrane, cell-to-cell adhesion, etc.

SCREEN PROTECTION BARRIER, improve barrier for mechanical stress/physical force

Question 17

How does cholera toxin work?

Answer 17

Cholera toxin binds to and enters cells that have GM1 (type of ganglioside) in their membranes and then causes increase in cAMP in the small intestine that leads to efflux of Na+ and water (diarrhea)

Question 18

Transmembrane proteins have both ______ and ______ regions, making them “_______”.

Answer 18

Transmembrane proteins have both hydrophobic and hydrophillic regions- amphiphilic.

Hydrophobic AA’s mostly interact with the core of the lipid bilayer. Hydrophillic AA’s (side chains containing polar oxygen and nitrogens) tend to locate on the outer and inner membrane/water interfaces.

Question 19

How are cytosolic and extracellular domains seperated?

Answer 19

Cytosolic and extracellular domains are seperated by the membrane spanning domains, which are composed largely of amino acids with nonpolar side chains.

Moreover, membrane proteins oragnize themselves in lipid bilayers in such a way as to maximize H bond interactions between polar groups forming regular alpha-helices

Question 20

How can you predict which part of a peptide chain extend across the lipid bilayer?

Answer 20

From the amino acid sequence, it is possible to predict which parts of the peptide chain extend across the lipid bilayer. Segments containing 20-30 amino acids with a high degree of hydrophobicity can span a membrane as an alpha helix, and they can be identified in a hydropathy plot.

Question 21

What is an alternative way for transmembrane proteins to pass a membrane?

Where is this structure located?

What is preferred structure in eukaryotes?

Answer 21

Formation of a beta sheet or a beta barrel is an alternative way for transmembrane proteins to pass a membrane. Hydrophilic AA’s will be inside the barrel. The beta barrel transmembrane proteins are limited to mitochondria, chloroplasts, and bacteria.

Cell prefers to use alpha helix in eukaryotes, more dynamic.

Question 22

Which phospholipid is involved in apoptosis?

Answer 22

Phosphatidylserine

Question 23

What is an important difference between proteins in the two sides of the membrane?

Answer 23

Important difference between proteins on the two sides of the membrane results from the reducing enviornment of the cytosol. Thus, disulfide (S-S) bonds will be formed only on the extracellular surface of the cell.

Question 24

Many membrane proteins are often _______ on their extracellular sides, and extensive ________ creates a ________.

What role does that structure play?

Answer 24

Many membrane proteins are often glycosylated on their extracellular sides, and extensive glycosylation creates a glycocalyx.

That glycocalyx plays a role to protect cells against mechanical and chemical damage.

Remember: Reductive inside cell (cytosol),

Oxidative outside cell

Question 25

Some membrane proteins diffuse along the ______, others are anchored via ________.

Answer 25

Some mebrane proteins diffuse along the bilayer plane, others are anchored via cytoskeleton proteins.

Question 26

Majority of the membrane proteins in eukaryotes are:

alpha helices or beta sheets?

Answer 26

Answer: majority of eukaryotic transmembrane proteins are ALPHA HELICES

Question 27

What plays the most important role in cell signaling?

What plays a role in apoptosis?

Answer 27

Cell signaling: phosphatidylinositol

Apoptosis: phosphatidylserine

(remember the PS gets moved from inside the cell to outside by the scramblase/translocator)