Macro Exam: Cell Membrane 1+2

boundaries, access, transport, energy, cell signaling, communication

Relevance of biological membranes

• Define ______ of cells 

• Control ______ and _____ of molecules

• Organize and divide intro discrete components

• Enable organisms to generate _____ 

• Platform for _____________ (transduction pathways) and __________

cell growth, movement, exocytosis, endocytosis, concentration, small, hydrophobic, large, polar

Cell Membrane features

• Helps with __________ and ______ 

• Crucial for _______ and ________ 

• Selective permeability (controls _________ of certain molecules inside the cell)

  • Only lets _____ and/or ________ molecules through by diffusion

  • ______ and/or _____ molecules have to enter by facilitated diffusion (membrane transport proteins or channels)

lipids, proteins, glycoproteins, glycolipids

Cell Membrane Composition

• Composed of _____ and ______ 

• Carbohydrates are present as part of _________ and _________ 

Cholesterol, Sphingolipids, and Glycerophospholipids

The major lipids in mammalian membranes

amphipathic

Phospholipids are ________ (have a hydrophilic and hydrophobic side)

Asymmetrical

Two sides of the membrane are _____________ (structurally and functionally)

composition, extracellular, cytoplasm, orientation, positioning, enzymatic activities

Two sides of the membrane are asymmetrical (structurally and functionally):

1. Different __________ of lipids, proteins and carbohydrates

• Phosphatidylcholine and sphingolipids on the ________ side

• Phosphatidylinositol and amino-phospholipids face the ________

2. Different _________ and ________ of the proteins 

3. Different _____________ of the two sides 

Phosphatidylcholine, sphingolipids

_______________ and ____________ are mostly found in the extracellular-facing side of the membrane

Phosphatidylinositol, amino-phospholipids

________________ and _________________  mostly face the cytoplasm.

lipid bilayer, bilayer

In the fluid mosaic model, a ___________ is the basic structural unit, and the proteins associate with or span the ________.

Integral membrane protein, phospholipid

____________________ “icebergs” floating in a sea of (predominantly) fluid __________ molecules.

Glycoprotein

Protein with carbohydrate attached

Glycolipid

Lipid with carbohydrate attached

polar hydroxyl, hydrophilic, hydrophobic

Cholesterol

• Insert into bilayer with ___________ group being attracted to _________ phosphate heads of phospholipids

• Non-polar tails attracted to __________ tails of phospholipids in the center of the membrane

Phosphatidylcholine

Generally the major phosphoglyceride by mass in the membranes of human cells

Unsaturated

Cis double bond is ________

heterogenous, lipid transfer proteins (LTPs), hydrophobic, monomeric, oligomeric, ATP driven

Intracellular Lipid Transfer 

• Lipids are distributed in a _________ fashion 

• Bulk of lipid traffic is mediated by a large group of ________________

• Move small # of lipids using _______ cavities to stabilize them outside the membrane (aqueous environment)

  • ________ LTP

  • _________ LTP

  • _________ LTP

post-translational, glycosylation, covalent attachment

Membrane Proteins 

• Have more extensive _____________ modification: 

  • ___________ ⇒ add carbohydrates

  • _________________ ⇒ adds lipids

Integral, Peripheral, and Amphitropic Proteins

Three groups of membrane proteins

Integral Proteins

Firmly embedded within the membrane, only removable by extreme processes (detergents)

Monotopic, bitopic, and polytopic

Types of Integral Proteins

Monotopic

Interacts with only a single leaflet (side) of membrane (small hydrophilic domains)

Bitopic

Span the bilayer once, have a single hydrophobic sequence in middle of the molecule (extends on both sides)

Polytopic

Span the bilayer several times, has multiple hydrophobic sequences spanning the bilayer

A-helix bundle

Parallel or antiparallel alpha helices, recognition and receptors (shaped by H-bonding)

B-barrel

Closed beta sheet around a central pore, transporters (channel proteins) (shaped by H-bonding)

Caveolins

A family of integral proteins, surface plasma-membrane flask-shaped structures 

Endocytosis, signaling platform, enlarging the cell

Functions of Caveolins

Peripheral Proteins

• Can bind to membrane by itself or attach to integrated proteins:

  • Via electrostatic interaction and/or hydrogen binding with hydrophilic domain of integrated proteins and charged head of membrane lipids 

• Can be separated from membrane by milder treatments 

Amphitropic proteins

• Associate reversibly with the membrane (can detach itself without treatment)

• Found associated with the membrane and in the cytoplasm

• Affinity to membrane is from non-covalent interaction with another membrane protein or lipid or the presence of one or more covalently attached lipids to the protein 

reversible, membrane-bound, soluble, C, polar head

Amphitropic Proteins:

• Lipid attachment process is _______ (when protein is lipid-linked = ___________, when protein is not lipid-linked = ________)

• Glycosylphosphatidylinositol (GPI) is an example of the anchor glycolipid. Phospholipase _ is an enzyme that removes the _________ group (including phosphate) from phospholipids.

non-covalent, fatty acids, higher, shorter, higher, temperature, cholesterol, hydrocarbon

Membrane fluidity 

• Fluidity due to __________ (less stiff) interaction among lipids

• Fluidity depends on:

  • __________ → More double bonds/unsaturation = _____ fluidity; _____ carbon chain = _____ fluidity 

  • Increased _______ = increased movement/fludity 

  • Higher ________ content = lower fluidity 

  • _________ bond of fatty acid = less fludity

Transbilayer diffusion

One side of membrane to another (↕), Very slow (days)

Lateral diffusion

Move positions sideways on same side of membrane (↔), Very fast (a second)

Catalyzed transbilayer translocation

Contains flippase, floppase, and scramblase

Flippase

moves phospholipid inward to cytosolic leaflet

Floppase

moves phospholipid outward to outer leaflet

Scramblase

moves lipids in either direction, toward equilibrium

diffuse laterally, anchored, prevent

Protein movement in membrane 

• Many membrane proteins are mostly free to __________ 

• Some membrane proteins are _______ to internal structures that ______ movement

Passive transport

Down an electrochemical gradient

Simple and Facilitated diffusion

Types of passive transport

Simple diffusion

small, hydrophobic molecules go through membrane due to concentration gradient

Facilitated diffusion

small, hydrophilic molecules/ions diffuse with the aid of channel or carrier protein according to concentration gradient

Channel proteins

Either open at all times OR they’re gated (chemically/ligand gated, voltage gated, mechanically/pressure gated)

Ion channels

Rate of transport is greater than transporters, NOT saturable

Transporters (pumps)

Rate of transport is well below limits of free diffusion, ARE saturable, highly specific for their substrates

Active transport

Against an electrochemical gradient and requires an input of energy,

Primary and Secondary transport

Types of active transport

Primary transport

Uses energy released by ATP hydrolysis

Na-K ATPase, 3 Na+, 2 K+, Na+, ATP

• Primary transport

  • ___________ (sodium potassium pump) is an antiport that drives cotransport of many other solutes (such as Na⁺-glucose symporter)

    • _____ ions out and _____ ions in → ATP converted to ADP

    • The gradient of ___ is used to drive the cotransport of solutes in many cell types

  • ___=S gradient, maintains electrochemical gradient in living cells

Secondary transport

Movement from gradient of an ion from primary active transport generates energy to drive cotransport of a second solute

Down, against

Secondary transport

• Movement of S1 ____ its electrochemical gradient provides energy to drive co-transport of a second solute, S2, ______ its electrochemical gradient

• Using gradient

Gap Junctions

Structures that permit direct transfer of small molecules (up to ~1200 Da) from one cell to its neighbor

connexins, 12, connexin, cellular

Gap Junctions (GJ)

• Composed of a family of proteins called _________ that form a bi-hexagonal structure consisting of such proteins (membrane-spanning _______ channel).

• Play a role in _______ communication

Uniport

Moves one type of molecule bidirectionally (transport systems), Ex: GLUT2 in intestinal epithelial cells

Symport

Moves two solutes in the same direction (transport systems), Ex: Na⁺-glucose symporter in intestinal epithelial cells

Antiport

Moves two molecules in opposite directions (transport systems), Ex: cardiac Na⁺/Ca²⁺ antiporter, Na⁺ in and Ca²⁺ out

Endocytosis

Moves particles like large particles, parts of cells, whole cells, INTO a cell

Phagocytosis, Pinocytosis, Receptor-mediated, and Caveolae

Types of Endocytosis

Phagocytosis

engulf/internalize large molecules

Pinocytosis

(invagination) cell membrane forms pocket and pinches off into cell to form vesicle filled with extracellular fluid and molecules

Receptor-mediated

(Clathrin) coated pits, endocytosis triggered

Caveolae

Flask-shaped pit that's pinched off the membrane, endocytosis triggered 

Exocytosis

contents of a cell vacuole/vesicle are released to EXTERIOR through fusion with the cell membrane, releases certain macromolecules from cells, involved in membrane remodeling, when the components are synthesized in the ER and Golgi are carried in vesicles that fuse in the plasma membrane

Constitutive, Regulated, and Lysosomal secretory pathway

Exocytosis secretary pathways

Constitutive secretory pathway

Operates continuously to deliver synthesized membrane and lipid proteins to membrane and also soluble proteins to be excreted into the extracellular pace and to other cells

Regulated secretory pathway

Found in specialized cells to secrete specific cargo, such as hormones, neurotransmitters, or enzymes

Lysosomal secretory pathway

Deliver extra membrane for repair, eject undigested debris out of the cell, and secrete cargo such as pigment (fusion of lysosomes with plasma membrane)

energy, ATP

Both endocytosis and exocytosis need _____ in the form of ___, used in the movement of substances in and out of the cell

inside, outside

Exocytosis involves the contact of two _____-surface (cytoplasmic side) monolayers, whereas endocytosis results from the contact of two _____-surface monolayers.

Depolarization, Ca2+, Ca2+, increase, exocytosis, neuron, muscle

Synapses

1. ___________ wave reaches axon tip → voltage gated ____ channels open, ____ enters the cell

2. ______ in intracellular Ca²⁺ concentration triggers ______ of NT into synaptic cleft

3. NT binds to receptor on post-synaptic _____/______ cell and causes ligand-gated channels to open

Cystic Fibrosis

• CF Transmembrane conductance regulator (CFTR) protein maintains salt-water balance

• Codes for ion channel protein that conducts Cl- and bicarbonate ions across membranes

• Mutations lead to dysregulation of epithelial lining fluid (mucus) in lungs and other organs = thickened mucus and infections

Cystinosis

• Rare, multisystem genetic disorder 

• Caused by mutations of CTNS gene (encodes cystinosin) 

• Disease of the lysosomal transporter which normally allows cysteine to reenter the cytosol