Ch05 Lecture-Cell Membranes and Signaling-1

5
Cell Membranes and Signaling
Concept 5.1 Biological Membranes Have a Common Structure and Are Fluid
A membranes structure and functions are determined by its constituents: lipids, proteins, and carbohydrates. The general structure of membranes is known as the fluid mosaic model. Phospholipids form a bilayer which is like a lake in which a variety of proteins float.
Figure 5.1 Membrane Molecular Structure
Lipids form the hydrophobic core of the membrane.
Most lipid molecules are phospholipids with two regions:

Hydrophilic regionselectrically charged heads that associate with water molecules Hydrophobic regionsnonpolar fatty acid tails that do not dissolve in water
A bilayer is formed when the fatty acid tails associate with each other and the polar heads face the aqueous environment.
Bilayer organization helps membranes fuse during vesicle formation and phagocytosis.
Membranes may differ in lipid composition as there are many types of phospholipids. Phospholipids may differ in:
Fatty acid chain length

Degree of saturation
Kinds of polar groups present
Two important factors in membrane fluidity:
Lipid compositiontypes of fatty acids can increase or decrease fluidity Temperaturemembrane fluidity decreases in colder conditions
Biological membranes contain proteins, with varying ratios of phospholipids. Peripheral membrane proteins lack hydrophobic groups and are not embedded in the bilayer. Integral membrane proteins are partly embedded in the phospholipid bilayer.
Anchored membrane proteins have lipid components that anchor them in the bilayer. Proteins are asymmetrically distributed on the inner and outer membrane surfaces. A transmembrane protein extends through the bilayer on both sides, and may have different functions in its external and transmembrane domains.
Some membrane proteins can move within the phosopholipid bilayer, while others are restricted. Proteins inside the cell can restrict movement of membrane proteins, as can attachments to the cytoskeleton.
Plasma membrane carbohydrates are located on the outer membrane and can serve as recognition sites. Glycolipida carbohydrate bonded to a lipid Glycoproteina carbohydrate bonded to a protein
Membranes are constantly changing by forming, transforming into other types, fusing, and breaking down. Though membranes appear similar, there are major chemical differences among the membranes of even a single cell.
Concept 5.2 Some Substances Can Cross the Membrane by Diffusion
Biological membranes allow some substances, and not others, to pass. This is known as selective permeability.
Two processes of transport:

Passive transport does not require metabolic energy. Active transport requires input of metabolic energy.
Passive transport of a substance can occur through two types of diffusion: Simple diffusion through the phospholipid bilayer Facilitated diffusion through channel proteins or aided by carrier proteins
Diffusion is the process of random movement toward equilibrium. Speed of diffusion depends on three factors: Diameter of the moleculessmaller molecules diffuse faster Temperature of the solutionhigher temperatures lead to faster diffusion
The concentration gradient in the systemthe greater the concentration gradient in a system, the faster a substance will diffuse
A higher concentration inside the cell causes the solute to diffuse out, and a higher concentration outside causes the solute to diffuse in, for many molecules.
Simple diffusion takes place through the phospholipid bilayer. A molecule that is hydrophobic and soluble in lipids can pass through the membrane. Polar molecules do not pass through they are not soluble in the hydrophilic interior and form bonds instead in the aqueous environment near the membrane.
Osmosis is the diffusion of water across membranes. It depends on the concentration of solute molecules on either side of the membrane. Water passes through special membrane channels.
Diffusion of water from HIGH concentration of water to LOW concentration of water across a semi-permeable membrane
Figure 5.3A Osmosis Can Modify the Shapes of Cells
Figure 5.3B Osmosis Can Modify the Shapes of Cells
Figure 5.3C Osmosis Can Modify the Shapes of Cells
SIMPLE DIFFUSION IS NOT ENOUGH
FACILITATED DIFFUSION
Channel proteins are integral membrane proteins that form channels across the membrane.
Substances can also bind to carrier proteins to speed up diffusion.
Examples
aquaporin = water channel in bacteria
Porin monomer
CHANNEL PROTEIN
H2 O
b-pleated sheets Bacterial outer membrane
H2O
function through conformational change = protein changes shape
Ion channels are a type of channel proteinmost are gated, and can be opened or closed to ion passage.

Carrier proteins in the membrane facilitate diffusion by binding substances. Glucose transporters are carrier proteins in mammalian cells. Glucose molecules bind to the carrier protein and cause the protein to change shapeit releases glucose on the other side of the membrane.
Biological Systems Still Need a Way of Maintaining Differences Across a Membrane AGAINST the Concentration Gradient THIS IS ACTIVE TRANSPORT
Concept 5.3 Some Substances Require Energy to Cross the Membrane
Active transport requires the input of energy to move substances against their concentration gradients. Active transport is used to overcome concentration imbalances that are maintained by proteins in the membrane.
The energy source for active transport is often ATP. Active transport is directional and moves a substance against its concentration gradient. A substance moves in the direction of the cells needs, usually by means of a specific carrier protein.
Two types of active transport:
Primary active transport involves hydrolysis of ATP for energy.

Secondary active transport uses the energy from an ion concentration gradient, or an electrical gradient.
The sodiumpotassium (Na+K+) pump is an integral membrane protein that pumps Na+ out of a cell and K+ in. One molecule of ATP moves two K+ and three Na+ ions.
Figure 5.7 Primary Active Transport: The SodiumPotassium Pump
Secondary active transport uses energy that is regained, by letting ions move across the membrane with their concentration gradients.
Secondary active transport may begin with passive diffusion of a few ions, or may involve a carrier protein that transports both a substance and ions.
Secondary Active Transport
Concept 5.4 Large Molecules Cross the Membrane via Vesicles
Macromolecules are too large or too charged to pass through biological membranes and instead pass through vesicles.
To take up or to secrete macromolecules, cells must use endocytosis or exocytosis.
Figure 7.22
Phagocytosis
EXTRACELLULAR FLUID Solutes
Pinocytosis
Receptor-Mediated Endocytosis
Pseudopodium Plasma membrane Ligand
Receptor
Coat proteins
Food or other particle
Coated pit Coated vesicle
Vesicle Food vacuole
CYTOPLASM
Concept 5.4 Large Molecules Cross the Membrane via Vesicles
Receptormediated endocytosis depends on receptors to bind to specific molecules (their ligands). The receptors are integral membrane proteins located in regions called coated pits. The cytoplasmic surface is coated by another protein (often clathrin).
Concept 5.5 The Membrane Plays a Key Role in a Cells Response to Environmental Signals
Cells can respond to many signals if they have a specific receptor for that signal. A signal transduction pathway is a sequence of molecular events and chemical reactions that lead to a cellular response, following the receptors activation by a signal.
SWITCH TO OTHER POWER POINT
Cells are exposed to many signals and may have different responses: Autocrine signals affect the same cells that release them.
Paracrine signals diffuse to and affect nearby cells. Hormones travel to distant cells.
Figure 5.10 Chemical Signaling Concepts
Only cells with the necessary receptors can respond to a signalthe target cell must be able to sense it and respond to it.
A signal transduction pathway involves a signal, a receptor, and a response.
Figure 5.11 Signal Transduction Concepts
A common mechanism of signal transduction is allosteric regulation. This involves an alteration in a proteins shape as a result of a molecule binding to it. A signal transduction pathway may produce short or long term responses.
A signal molecule, or ligand, fits into a three-dimensional site on the receptor protein. Binding of the ligand causes the receptor to change its three-dimensional shape. The change in shape initiates a cellular response.
Figure 5.12 A Signal Binds to Its Receptor
Ligands are generally not metabolized further, but their binding may expose an active site on the receptor. Binding is reversible and the ligand can be released, to end stimulation. An inhibitor, or antagonist, can bind in place of the normal ligand.
Receptors can be classified by their location in the cell. This is determined by whether or not their ligand can diffuse through the membrane.
Cytoplasmic receptors have ligands, such as estrogen, that are small or nonpolar and can diffuse across the membrane. Membrane receptors have large or polar ligands, such as insulin, that cannot diffuse and must bind to a transmembrane receptor at an extracellular site.
Receptors are also classified by their activity: Ion channel receptors Protein kinase receptors G proteinlinked receptors
Ion channel receptors, or gated ion channels, change their threedimensional shape when a ligand binds. The acetylcholine receptor, a ligandgated sodium channel, binds acetylcholine to open the channel and allow Na+ to diffuse into the cell.
Protein kinase receptors change their shape when a ligand binds. The new shape exposes or activates a cytoplasmic domain that has catalytic (protein kinase) activity.
Figure 5.13 A Protein Kinase Receptor
Protein kinases catalyze the following reaction: ATP + protein ADP + phosphorylated protein Each protein kinase has a specific target protein, whose activity is changed when it is phosphorylated.
Ligands binding to G proteinlinked receptors expose a site that can bind to a membrane protein, a G protein. The G protein is partially inserted in the lipid bilayer, and partially exposed on the cytoplasmic surface.
Many G proteins have three subunits and can bind three molecules: The receptor GDP and GTP, used for energy transfer An effector protein to cause an effect in the cell
The activated G proteinlinked receptor exchanges a GDP nucleotide bound to the G protein for a higher energy GTP. The activated G protein activates the effector protein, leading to signal amplification.
Figure 5.14 A G ProteinLinked Receptor
Concept 5.6 Signal Transduction Allows the Cell to Respond to Its Environment
Signal activation of a specific receptor leads to a cellular response, which is mediated by a signal transduction pathway.
Signaling can initiate a cascade of protein interactionsthe signal can then be amplified and distributed to cause different responses.
A second messenger is an intermediary between the receptor and the cascade of responses. In the fight-or-flight response, epinephrine (adrenaline) activates the liver enzyme glycogen phosphorylase. The enzyme catalyzes the breakdown of glycogen to provide quick energy.
Researchers found that the cytoplasmic enzyme could be activated by the membrane-bound epinephrine in broken cells, as long as all parts were present.
They discovered that another molecule delivered the message from the first messenger, epinephrine, to the enzyme.
Figure 5.15 The Discovery of a Second Messenger (Part 1)
Figure 5.15 The Discovery of a Second Messenger (Part 2)
The second messenger was later discovered to be cyclic AMP (cAMP). Second messengers allow the cell to respond to a single membrane event with many events inside the cellthey distribute the signal. They amplify the signal by activating more than one enzyme target.
Figure 5.16 The Formation of Cyclic AMP
Signal transduction pathways involve multiple stepsenzymes may be either activated or inhibited by other enzymes. In liver cells, a signal cascade begins when epinephrine stimulates a G proteinmediated protein kinase pathway.
Epinephrine binds to its receptor and activates a G protein. cAMP is produced and activates protein kinase Ait phosphorylates two other enzymes, with opposite effects: Inhibition
Activation
Figure 5.17 A Cascade of Reactions Leads to Altered Enzyme Activity (Part 1)
Figure 5.17 A Cascade of Reactions Leads to Altered Enzyme Activity (Part 2)
Inhibitionprotein kinase A inactivates glycogen synthase through phosphorylation, and prevents glucose storage.
ActivationPhosphorylase kinase is activated when phosphorylated and is part of a cascade that results in the liberation of glucose molecules.
Signal transduction ends after the cell respondsenzymes convert each transducer back to its inactive precursor. The balance between the regulating enzymes and the signal enzymes determines the cells response.
Figure 5.18 Signal Transduction Regulatory Mechanisms
Cells can alter the balance of enzymes in two ways: Synthesis or breakdown of the enzyme Activation or inhibition of the enzymes by other molecules
Cell functions change in response to environmental signals: Opening of ion channels Alterations in gene expression Alteration of enzyme activities
Answer to Opening Question
Caffeine is a large, polar molecule that binds to receptors on nerve cells in the brain. Its structure is similar to adenosine, which binds to receptors after activity or stress and results in drowsiness.
Caffeine binds to the same receptor, but does not activate itthe result is that the person remains alert.
Figure 5.19 Caffeine and the Cell Membrane (Part 1)
Figure 5.19 Caffeine and the Cell Membrane (Part 2)

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5

Cell Membranes and Signaling

Figure 5.1 Membrane Molecular Structure

Lipids form the hydrophobic core of the membrane.

Most lipid molecules are phospholipids with two regions:

Fatty acid chain length

Kinds of polar groups present

Two important factors in membrane fluidity:

Concept 5.2 Some Substances Can Cross the Membrane by Diffusion

Two processes of transport:

Concept 5.2 Some Substances Can Cross the Membrane by Diffusion

Concept 5.2 Some Substances Can Cross the Membrane by Diffusion

Concept 5.2 Some Substances Can Cross the Membrane by Diffusion

Concept 5.2 Some Substances Can Cross the Membrane by Diffusion

Concept 5.2 Some Substances Can Cross the Membrane by Diffusion

Figure 5.3A Osmosis Can Modify the Shapes of Cells

Figure 5.3B Osmosis Can Modify the Shapes of Cells

Figure 5.3C Osmosis Can Modify the Shapes of Cells

SIMPLE DIFFUSION IS NOT ENOUGH

Concept 5.2 Some Substances Can Cross the Membrane by Diffusion

function through conformational change = protein changes shape

Concept 5.2 Some Substances Can Cross the Membrane by Diffusion

Concept 5.2 Some Substances Can Cross the Membrane by Diffusion

Concept 5.3 Some Substances Require Energy to Cross the Membrane

Concept 5.3 Some Substances Require Energy to Cross the Membrane

Concept 5.3 Some Substances Require Energy to Cross the Membrane

Two types of active transport:

Primary active transport involves hydrolysis of ATP for energy.

Concept 5.3 Some Substances Require Energy to Cross the Membrane

Figure 5.7 Primary Active Transport: The SodiumPotassium Pump

Concept 5.3 Some Substances Require Energy to Cross the Membrane

Secondary Active Transport

Concept 5.4 Large Molecules Cross the Membrane via Vesicles

To take up or to secrete macromolecules, cells must use endocytosis or exocytosis.

Pseudopodium Plasma membrane Ligand

Food or other particle

Coated pit Coated vesicle

Vesicle Food vacuole

Concept 5.4 Large Molecules Cross the Membrane via Vesicles

SWITCH TO OTHER POWER POINT

Figure 5.10 Chemical Signaling Concepts

A signal transduction pathway involves a signal, a receptor, and a response.

Figure 5.11 Signal Transduction Concepts

Figure 5.12 A Signal Binds to Its Receptor

Figure 5.13 A Protein Kinase Receptor

Figure 5.14 A G ProteinLinked Receptor

Figure 5.15 The Discovery of a Second Messenger (Part 1)

Figure 5.15 The Discovery of a Second Messenger (Part 2)

Figure 5.16 The Formation of Cyclic AMP

Figure 5.17 A Cascade of Reactions Leads to Altered Enzyme Activity (Part 1)

Figure 5.17 A Cascade of Reactions Leads to Altered Enzyme Activity (Part 2)

Figure 5.18 Signal Transduction Regulatory Mechanisms

Answer to Opening Question

Figure 5.19 Caffeine and the Cell Membrane (Part 1)

Figure 5.19 Caffeine and the Cell Membrane (Part 2)

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