BIOC 405 Unit 2

What are the 4 primary fx of biological membranes in eukaryotic cells

1. Defining cell and organelle boundaries

2. selectively permeable membranes for molecules and signaling

3. maintaining electrochemical/concentration gradients for energy storage and transport

4. allowing later diffusion, vesicle formation, and membrane fusion

Which eukaryotic cell is an exception to being packed with multiple organelles

RBCs

Which structurual component determines the physical properties of membrane lipids like glycerophospholipids and sphinglipids

fatty acyl chains

What main cellular organelle is responsible for synthesizing lipids and modifying new polypeptide chains

smooth ER

Why must biological membranes be self-sealing and flexible

to adapt to varying cellular shapes, accomodate diverse proteins, and maintain concentration gradients

What structural feature do cis-double bonds introduce into the hydrocarbon chain of an unsaturated fatty acid and what is the angle

30 degree kink in the chain

How are carbons labeled relative to the carboxyl carbon and the opposite end in fatty acid nomenclature

start at C bound to O and count towards the methyl tail end

How to label carbons based on omega carbon system

start at terminal methyl end count to carbonyl carbon

Between stearate (18:0) and oleate (18:1cdelta9), which has a lower melting point

18:1cdelta9, because it's cis double bond creates a kink that prevent tight molecular packing

Do naturally occuring unsat fatty acids predominately feature cis/trans double bonds and are these double bonds conjugated

cis and non-conjugated, and even number of carbons

What are the basic chemical components combined to form lipids like triacylglycerols and phospholipids

backbone including glycerol/L-serine, fatty acid tails, phosphate groups, and polar head groups

What thermodynamic driving force causes lipids to self-associate and form bilayers in aqueous solution

hydrophobic effect which minimizes contact between hydrophobic hydrocarbons and water to maximize entropy

What are cardiolipins and where are they located in the cell

double phosphoglycerides with 4 fatty acid tails, make up inner mitochondrial membranes and act as an insulator to stabilize ETC

What is the parent compound for more abundant sphingolipids and from which two molecules is is synthesized from

Ceramide: combines serine and palmitate (sphingosine) + fatty acid

What are sphingomyelins

Sphingolipids where the head group is phosphocholine or phosphoethanolamine. (so NH3 group or chlorine group)

What are gangliosides?

Ceramides linked to branched sugars + sialic acid, involved in signaling

What are cerebrosides

Glycosphingolipids with one sugar

What core ring structure is shared by all sterols/steroids and what the two major roles of cholesterol derivatives

4 fused non-planar rings, 3 6 member and 1 5 members

Cholesterol derivatives serve as steroid hormones for signaling and bile salts for digestion

What properties of phospholipids promote the self-assembly of lipid bilayers

amphipathic properties

What types of lipids form micelles

single tail lipids that form restricted micelles (single fatty acyl chains)

what types of lipids form bilayers

cyclinderacal such as phosphoglycerides

what is the difference in lateral diffusion rates between lipid and integral membrane proteins

lipids diffuse faster compared to integral proteins

what is the symmetry of the fluid mosaic model

asymetric

what method is used to determine lateral diffusion rates of lipids and proteins in biological membranes

FRAP: lipids labeled with fluorescent molecules, laser bleaches a certain area dark and we moniter the recovery of the fluoresences within the bleached area which indicates movement of membrane

What role does temperature play in phospholipid membranes

increased temp increased fluidity and decreased temp decreases fluidity

What are the factors affecting membrane fluidity

fatty acid tail length: shorter lengths increase fluidity at lower temps and longer lengths decrease fluidity at higher temps

sat. vs. unsat.: unsat. increase fluidity at lower temps and sat. decrease fluidity at higher temps

How do eukaryotes use cholestrol

regulate membrane fluidity

more cholestrol lowers fluidity- at higher temps

less cholestrol increases fluidity- at low temps

How does cholesterol pack with lipids

does not form a bilayer on its own and tends to associate with longer sat. fatty acyl tails (makes sense as more cholestrol tends to decrease fluidity)

What are lipid rafts and what lipid classes are they primarily enriched in?

ordered microdomains enriched in cholestrol and sphingolipids (longer saturated tails) that serve as platforms for signaling and membrane budding, they are also thicker than the rest of the membrane

Which phosphplipids are found in the outer leaflet and which are found in the inner leaflet

outer: cerebrosides & gangliosides (phosphatidylcholine)

inner: phosphatidylethanolamine (indicates cell death on outside)

What type of diffusion is very slow

lateral diffusion

How does the membrane overcome the energy barrier of transverse diffusion

lipid transporter proteins

What are the 3 types of lipid translocating proteins that maintain membrane asymmetry

1. Flippase- P-type ATPases (outside to inside)

2. Floppase- ABC transporters (inside to outside)

3. Scramblases- does not require energy and driven by concentration gradients

Two general classes of membrane proteins

1. Integral (contacts with hydrophobic regions, span bilayer, only 1 orientation

2. peripheral (interacts with exposed surfaces)

How many amino acids are required in an alpha helix to span the membrane and what type of side chains are exposed to lipids

20, exposing hydrophobic side chains

Where are beta barrel integral membranes typically found

outer membranes of mitochondria, chloroplasts, and bacteria

What are annular lipids and what structural function do they perform around integral membrane proteins

surround hydrophobic protein surface, acyl groups adapt to the grooves of the proteins and provide smooth self-annealing transition surface for the bulk lipids

Which lipid anchor modification are found on the cytoplasmic side vs. the extracellular side of the plasma membrane

cytoplasmic side: fatty acylation (myristate, palmitate) and prenylation w/raft (farnesyl and geranylgeraniol)

extracellular side w/ lipid rafts: GPI anchors

what structural sequence motif at the C-terminus typically signals for protein prenylation

CAAX box

what specialized membrane domain is formed with caveolin dimers associate with lipid rafts to induce membrane invagination

caveola

what filametous cytoskeleton proteins forms the primary sub-membrane network responsible for maintaining the shape of RBCs

actin and spectrin (a and b) anchor to integral proteins

How does today's understanding of the fluid mosaic model differ from the original 1972 model regarding membrane protein and lipid organization

today's model includes lipid rafts, cytoskeletal fencing (which restricts lateral diffusion), membrane crowding (high protein density), and clusters of glycosylated proteins--continually evolving

What is used to determine the free energy change for transporting an uncharged molecules across a membrane

only concentration C2/C1 where C1>C2

How does the equation for delta G change when transporting a charged molecule across a membrane

electrostatic term is added, delta V and charge of ion

why do ions have extremely low passive permeability across lipid membranes

Desolvation cost is too high to enter the hydrophobic core of the lipid bilayer

Despite being polar, water readily crosses lipid bilayers, why?

water is small and is present at high concentration so the movement is driven by osmotic pressure

what is the difference between active transport, passive, and facilitated diffusion

active transport moves stuff against their gradient which requires ATP

passive diffusion moves stuff down their concentration gradient

facilitated diffuion also moves stuff down concentration gradient but with some help such as ion channels (selective permeability)

Example of selective permeability

potassium channel: pore lines with backbone carbonyls to solvate K+

Aquaporins

channel proteins that facilitates passage of water, tetramer with 4 2.8 A pores, equalizes osmotic pressure with disrupting ionic gradients, displays sat. behavior

Glut permeases are...

passive glucose transporters , 12 membrane spanning helices, switches between 2 conformations, so never open, erthrocytes

How many ATPs does P type ATPase use and what does it drive

1, phosphorylation and dephosphorylation of ASP residue, two conformation (E1 open to cytoplasm, E2 open to outside)

eg. Ca2+, Na+/K+

How many ATPs does ABC transporters use and what does it drive

2, cause multi-drug resistance+CF, also undergoes conformational change

What are the 4 features common to biological signal transduction systems

1. Modularity

2. specificity

3. amplification

4. termination

How many transmembrane helices characterizes GPCRs

7

What causes the termination event of the G-protein signaling, and what enzymatic property terminates it

exchange of GTP for GDP, terminated by slow GTP hydrolysis which reassembles inactive complex

types of second messengers activated by GPCR

Cyclic AMP, IP3, DAG, calcium ions, phospholipase C

what enzyme does phospholipase C act upon during GPCR signaling and which two 2nd messengers are produced

PIP2 to produce IP3 which enters cytoplasm and DAG which stays in membrane

What change occurs in the insulin receptor kinase domain upon auto-phosphorylation and what effect does it have?

phosphorylation of Tyr residue from insulin (ligand) binding to receptor extracellularyly forces the activation loop to be in open conformation which triggers cascase (PIP 3) that causes GLUT4 vesicles to fuse with membrane and increase glucose uptake into cell

a single cardiolipin is made up of how many glycerols and how many phophates

3, 2

3 events that facilitate diffusion

ligand binding, temp. change, voltage

describe mechanism behind P-type ATPases

1. ATP binds to E1 state

2. ATP P-group attached to Asp->E2 state

3. Pump opens releasing substrate

4. Asp hydrolyzes

5. reverts back to E1

List the steps of information transfer via a G-protein coupled receptor

1. agonist binds receptor

2. G-protein binds->GDP/GTP exchange

3. alpha-beta unit dissociate from GTP to do work

4. slow GTP hydrolysis -> G protein inactivation

Difference between receptor tyrosine kinase and GPCR

TK: autophosphorylates from ligand binding

GPCR: activates trimeric GTP and signaling using secondary messengers

What proteins alternate between an "outward open" to "inward open" conformation

GLUT1, Ca2+ ATPase (SERCA)

Which proteins adopt C4 Symmetry

K+ ion channel

Aquaporins

in terms of chirality, which sugar enantiomers are more common

D

Why are there generally more aldohexoses and ketohexoses

ketohexoses have 1 less chiral center

How can you tell if a sugar is non-reducing vs. reducing

non-reducing: is closed in a glycosidic bond

reducing: anomeric carbon open and not in a bond

Difference between a and b anomeric carbons

b-up

a-down

constitutional isomers

same formula but different connnectivity

enantiomers

non-super imposable mirror images

Diasteoreomers

non mirror images

epimers

isomers differing at 1 chiral center

anomers

isomers that differ at a new asymmetric carbon atom formed on ring closure (a and b)

rank the polysaccharides from least to greatest number of reducing ends

glycogen, amylopectin, cellulose, and amylose

what type of linkage is at branch points and which linkage is at linear points

branch points: a-1,6

Linear points: a-1,4

How do branch points impact the number of non-reducing and reducing point of a polymer

non-reducing going up

reducing stays the same