Lecture 3 - Cell membrane and Signalling Flashcards
What are some major functions of membranes
Selective barrier to the passage of molecules
Detecting chemical signals from other cells
Anchoring cells to adjacent cells and to the extracellular matrix of connective-tissue proteins
What are the two classes of membrane proteins
Integral and peripheral
What are integral membrane proteins
closely associated with the membrane lipids, cannot be
extracted from the membrane without disrupting the lipid bilayer, and are amphipathic. Most
span the entire membrane and are referred to as transmembrane proteins.
What are peripheral membrane proteins
re not
amphipathic and do not associate with the
nonpolar regions of the lipids in the interior of
the membrane. They are located at the
membrane surface where they are bound to the
polar regions of the integral membrane proteins
How are cells joined
Desmosomes
Tight Junctions
Gap junctions
What are integrins
transmembrane
proteins in the plasma membrane
which bind to specific proteins in
the extracellular matrix and link
them to membrane proteins on
adjacent cells (e.g. CD11a)
What fills the gaps between cells
Interstitial fluid
What are desmosomes
Characterised by accumulations of
protein known as dense plaques along
the cytoplasmic surface of the plasma
membrane.
These proteins serve as anchoring points
for cadherins.
What is the function of a desmosome
hold adjacent cells firmly
together in areas that are subject to
considerable stretching, such as the skin.
What are cadherins
Cadherins are proteins that extend
from the cell into the extracellular
space, where they link up and bind
with cadherins from an adjacent cell.
What are tight junctions
Form when the extracellular surfaces of
two adjacent plasma membranes join
together so that no extracellular space
remains between them.
Unlike the desmosome, which is limited
to a disk-shaped area of the membrane,
the tight junction occurs in a band around
the entire circumference of the cell.
What are gap junctions
Consist of protein channels linking
the cytosols of adjacent cells.
Connexins from the two membranes
join, forming small, protein-lined
channels linking the two cells
What is diffusion
the movement of molecules from one location to another as a
result of their random “thermal motion
What is net flux
reflects the movement of material
from one compartment to another
How does temperature affect the magnitude of flux
higher = greater speed of molecular movement and greater net flux
How does the mass of a molecule affect the magnitude of a flux
molecules with a greater mass have a lower speed and smaller net flux
How does surface area affect magnitude of flux
the greater the surface area between the two regions the greater the space for
diffusion and the larger the net flux
how does the medium of which particles are moving through affect the magnitude of flux
molecules move quicker through air for example
What is the major factor limiting diffusion across a membrane
The hydrophobic interior
of its lipid bilayer
What are some properties of non polar molecules and examples
Oxygen, carbon dioxide, fatty acids, and steroid hormones
molecules that diffuse rapidly through the lipid portions of membranes
What are lipophilic molecules
Lipid-loving or hydrophobic substances that move through membranes easily
What are some properties of polar molecules
Hydrophilic, hence do not diffuse readily through the membrane
What are protein channels
integral membrane
proteins that span the lipid bilayer
A single protein may have a conformation
that looks like a doughnut, with the hole
in the middle providing the channel for
ion movement.
More often, several proteins
aggregate, each forming a subunit of
the walls of a channel.
for eg. Na+, K+, Cl-, Ca2+
What is channel specificity determined by
Pore size
Charge
Binding sites
What are the types of gated channels
Ligand
Voltage
Mechanically
What is a ligand gated channel
a specific molecule binds to the
channel causing an allosteric or covalent
change in the shape of the protein
- These ligands are often called chemical
messengers
What are voltage gated channels
Changes in the membrane potential
cause a movement of charged areas of
the protein altering its shape
What are mechanically gated channels
- Physically deforming (stretching)
the protein changes its
conformation
What are protein transporters
Many molecules (like glucose) are either
too large and charged to get into the cell
without help.
The protein transporters (also called
carriers) bring these molecules into and
out of cells by conformation changes.
What are the factors that determine the magnitude of solute flux through a mediated system
1) Saturation of transport binding sites:
in turn influenced by solute concentration and affinity of the
transporter for the solute
2) Number of transporters in the membrane
3) Rate at which the conformational change occurs
What are the two types of mediated transport systems
Facilitated diffusion
Active transport
What is facilitated diffusion
Facilitated diffusion is the net flux of a
molecule across a membrane from a higher
concentration to a lower concentration until
the concentration of the solute is equal
between the sides of the membrane
What is active transport
uses energy to move
molecules against the concentration gradient.
What are the types of energy source that can drive pumps
ATP in primary active transport
Use of an electrochemical gradient across a membrane to drive the process in secondary active transport
What is membrane potential
the separation of electrical charge across a membrane
What is the direction and magnitude of ion flux dependent on
- the concentration difference
- and the electrical difference
This is known as the electrochemical
gradient across the membrane
Describe the events in primary active transport
ATP is hydrolysed by an ATPase protein transporter: Na+/K+
- ATPase best studied
In turn, the transporter is phosphorylated
This type is a type of covalent modulation
…and this causes a conformational change in the molecule
… increasing the affinity of the solute binding site (slide 25)
Describe the events of secondary active transport
handout… label it!
However, rather than using
ATP, secondary active
transport uses the
electrochemical gradient to
transport solutes against the
concentration gradient
- Low Na+/high solute inside cell
- Electrochemical gradient directs
Na+ into the cell - Na+ binds to one site, the solute
binds to another - As Na+ is released into the cell,
so is the solute
How is the movement of water mediated
Aquaporins - family of membrane protein
How can aquaporin type and number vary
Thus, some membranes are more permeable to water
In some cells, the number of aquaporin channels
can be altered in response to certain signals:
important for re-absorbing water in the kidneys
DIRECTED READING - CHAPTER 4 VANDERS
What is a ligand
any molecule or ion that is bound to a protein by one of the
following forces:
(1) Electrical attractions between oppositely charged ionic or polarised groups on
the ligand and the protein
(2) Weaker attractions due to hydrophobic forces between nonpolar regions on
the two molecules
Generally reversible, doesn’t involve covalent bonds
What is chemical specificity
he ability of a protein binding site to
bind specific ligands
… because the binding site determines the type of
chemical or LIGAND that is bound.
In order to bind properly proteins must
have the correct conformational shape.
What is affinity
The strength of ligand-protein binding is a property of the binding site
How does affinity/binding strength affect the outcome of a reaction
Strong binding: site containing a positively
charged amino acid side chain.
Less-strong binding: A site having the same
shape but no positive charge.
Weaker binding: Different shape, no positive
charge
What is saturation
the fraction of total binding sites that are occupied at any given time
What are the factors that control percentage saturation
- The concentration of unbound ligand in the solution
- The affinity of the binding site for the ligand.
What are the 2 ways to control protein activity
- Changing protein shape – alters the binding of ligands
- Regulating protein synthesis and degradation (break down)
What are the 2 mechanisms in cells that selectively alter protein shape
. Allosteric modulation
2. Covalent modulation
What is allosteric modulation
protein has two binding sites and the binding
of a protein to one of the sites alters the shape of the other.
What is cooperativity
When a ligand binds to the first of several functional sites on a
molecule, this induces a change that increases the affinity of other functional sites
Describe the mechanism of allosteric mechanism (slide 47)
One binding site on an allosteric protein, known as the functional (or active) site, carries out the protein’s
physiological function.
The other binding site is the regulatory site.
Ligand that binds to regulatory site is a modulator molecule- its binding modulates the shape,
and therefore the activity, of the functional site.
What is covalent modulation
the covalent bonding of charged chemical groups to
some of the protein’s side chains
What is the most common type of addition in covalent modulation
De/Phosphorylation
A kinase is an enzyme that adds the phosphate
group to another protein.
A phosphatase is an enzyme that removes the
phosphate group from a protein
What does the metabolism consisting of
Catabolism: the breakdown of organic molecules
Anabolism: the synthesis of organic molecules
EXTRA RESOURCE ON MOODLE _ BREAKING CHEMICAL BONDS
What is activation energy
energy to
overcome the mutual repulsion
from electrons surrounding the
atoms that need to bump into
each other
What is law of mass action
the concentration of reactants
or products can determine the direction at which
the net reaction proceeds
What is an enzyme - long and basic
Enzymes are protein molecules, so an enzyme can be defined as a protein catalyst.
Enzymes lower the activation energy and make biological reactions proceed at a
higher reaction rate.
To function, an enzyme must come into contact with reactants (called substrates in
enzyme-mediated reactions).
The region of the enzyme that the substrate binds to: the active site
What is a cofactor
Most enzymes are inactive without small amounts of other substances: cofactors
Many cofactors are trace metals such as: magnesium, iron, zinc, copper.
Binding of a metal to an enzyme alters conformation so that it can bind to
the substrate– allosteric regulation
What is a coenzyme
An organic molecule that directly participates as one of the substrates in the reaction
Usually derived from vitamins eg. NAD and FAD
What are the 3 main factors affecting enzyme-mediated reactions
1) Substrate concentration
2) Enzyme concentration
3) Enzyme activity
What is maximal rate
all of the
active sites become occupied by substrate
What is it called when the product of an enzyme controlled reaction inhibits a part of the sequence
Feedback inhibition