Cell Physiology Flashcards
Cell
- structural and functional unit of all living organism
- smallest unit that can carry on all of life’s processes
Basic Components of the cell
- Plasma (cell) membrane- surrounds the cell surface
- Cell organelles- compartmentalize the cell and perform specific functions.
- Interior of the cell which consists of the nucleus and the cytoplasm.
Cell organelles can be _______ or _________
membrane-bound or non-membrane bound
Cytoplasm
the region outside the nucleus and is composed of cytosol, a gel-like fluid, in which the cell organelles are suspended.
Nucleus
- largest organelle in the cell
- houses the genetic material
Functions of the plasma (cell) membrane
(4)
- Physical barrier between the ICF and ECF fluids.
- keeps organelles and proteins inside cell
- maintains difference in ion composition between ICF and ECF
- maintains homeostasis -things may change outside the cell but inside remain constant. - Cell-to-cell communication
- contains receptors which bind signaling molecules. - Structural support
- contains connections composed of proteins which anchor cells to each other or to extracellular materials. - Transport
- plasma membrane is selectively permeable.
Explain how the plasma membrane is selectively permeable
some substances may simply move across the plasma membrane but most require specific transport proteins (transporters, carriers, channels etc.) to cross. It is therefore selectively permeable, allowing certain molecules to move across but not others.
The cell/plasma membrane and the intracellular membranes surrounding organelles are composed of a ________________ with embedded proteins.
double layer of lipid molecules
Phospholipid bilayer
2 layers of phospholipids with embedded proteins
_________ membranes have different ratios of lipids and proteins.
Biological
Amphipathic molecule
- contains polar and nonpolar regions
- biological membrane lipids (cell/plasma membrane and membranes surrounding organelles) are amphipathic.
Amphipathic lipids found in biological membranes include __________, _________, and ________
phospholipids, cholesterol, glycolipids
Structure of a phospholipid
- Polar head group: phosphate attached to glycerol, a nitrogen-containing chemical group, and glycerol backbone.
- polar head group is hydrophilic (water-loving or dissolves in water) - Nonpolar tail: 2 fatty acid chains composed of carbon and hydrogen atoms.
- fatty acid chains may be: saturated (no double bonds) or unsaturated (containing 1 or more double bonds)
- nonpolar tail is hydrophobic (water-fearing or does not dissolve in water)
Structure of a phospholipid bilayer
Phospholipids spontaneously form bilayer when put in water.
- polar heads face aqueous environment, either the ECF or ICF
- nonpolar tails form hydrophobic core
- bilayer is the structure of the plasma membrane and the organelle membranes.
Cholesterol
- steroid lipid
- amphipathic
Nonpolar groups: carbon-hydrogen rings and a carbon-hydrogen chemical group attached to one of the rings.
Polar group: hydroxyl group - found in the cell/plasma membrane
- Very important part of the plasma membrane: there is almost one molecule of cholesterol for each molecule of phospholipid in the cell/plasma membrane (organelle membranes contain very little cholesterol
Function of cholesterol
maintains proper membrane fluidity
Glycolipids
- lipids with CHO (carbohydrate) attached
- found in the outer leaflet of the plasma membrane
- amphipathic due to presence of sugar
- form the glycocalyx
Glycocalyx
a layer of carbohydrates linked to lipids or membrane proteins
identification and interaction between cells
2 types of membrane proteins
- Integral (intrinsic)
- Peripheral (extrinsic)
Integral (intrinsic) membrane protein
- amphipathic -inserted into phospholipid bilayer of plasma/cell membrane and partially span membrane or are transmembrane proteins (completely cross phospholipid bilayer of membrane)
- comprise the majority (70%) of all proteins
- examples: transporters or channels
Peripheral membrane protein
- not amphipathic
- attached at the outer or inner surface of the membrane ( do not penetrate into the phospholipid bilayer
Glycoproteins
- Carbohydrates may be attached to proteins facing the extracellular surface of the plasma membrane and these are called glycoproteins. Form the glycocalyx along with glycolipids
Proteins are distributed _________ between the two halves of the plasma membrane and this is related to the function of the protein.
unequally
Ie. a receptor in the membrane has binding sites facing the ECF so signally molecules may arrive at the cell and bind to their receptors. These binding sites do not face inside the cell.
Cell junctions
specialized connections that stabilize interactions and promote communication between cells.
Desmosomes
- adhering junctions that anchor cells together in tissues subject to considerable stretching or mechanical stress
ie. heart muscle, uterus, skin - maintain structural integrity of tissue
- made of proteins called: plaques, cadherins, intermediate filaments
Plaques
- on cytoplasmic surface of the cell
- anchor cadherins
Cadherins
link cells together
Intermediate filaments
anchor cytoplasmic surface of desmosome to components inside cell to provide structural support
ie. keratin
Tight junctions
- found in epithelial tissue specialized for molecular transport
- made of proteins called occludins
Occludins
- form nearly impermeable junctions
- link adjacent cells together
- limit the movement of molecules between cells, forcing molecules to pass through the cell, or cross the plasma membrane (molecules can only cross the plasma membrane if they can diffuse through the lipid bilayer or have specific proteins in the membrane)
- limit the movement of integral membrane proteins and lipids
Gap junctions
- transmembrane channels linking the cytoplasm of adjacent cells
- made of proteins called connexons
- electrically and metabolically couple cells
electrically= allows ions to move between cells
metabolically= allow small molecules such as nutrients to move between cells - called communicating junctions as ions and molecules can move from one cell through the gap junction proteins (connexons) to another cell.
Functions of nucleus
- transmission of genetic information to next generation of cells
- contains the information needed for protein synthesis
The nucleus contains: (4)
- Chromatin -DNA and associated proteins
- Nuclear envelope -double layered porous membrane surrounding nucleus (composed of 2 phospholipid bilayers)
- Nuclear pores -pores in the nuclear envelope that allow molecules to move in and out of the nucleus
- Nucleolus -site of synthesis of ribosomal RNA
Structure of the nucleus
- nuclear envelope is made of 2 phospholipid bilayers, the inner and outer phospholipid bilayer
- nuclear envelope has nuclear pores
Watery channels made from proteins which allow molecules to move in and out of the nucleus (DNA too large to pass through the nuclear pores and remains in the nucleus)
Most cells have one nucleus except:
- Red blood cells -no nucleus
- Skeletal muscle -many nuclei in one skeletal muscle cell (multinucleate)
Ribosomes
- not surrounded by phospholipid bilayer
- function: protein synthesis
- composed of a small and large subunit
Large and small subunit of ribosome
- they are not functional when separate
- join to form a functional ribosome, or one capable of protein synthesis
- functional ribosomes may be found free in the cytoplasm or bound to the rough ER -proteins made in the cytoplasm have a different final destination in the cell than those made at the RER.
Endoplasmic reticulum (ER)
- fluid filled membranous system
- 2 types: rough ER and smooth ER
Rough endoplasmic reticulum (RER)
- flattened sacs with ribosomes attached to outer surface
- synthesizes proteins and performs post-translational modifications needed to produce a functional protein
Smooth endoplasmic reticulum (SER)
- branched tubular structure with no ribosomes attached to outer surface
- synthesizes lipids, stores calcium (in muscle; called the sarcoplasmic reticulum), drug detoxification (in liver)
Golgi apparatus
- composed of cisternae (flattened sacs)
- receives vesicles which contain proteins that were made at the RER
Functions of Golgi apparatus
- post-translational modifications of proteins made at the RER
- sorts and packages proteins into vesicles
- proteins in these vesicles may be: secreted from the cell, become integral membrane proteins, or become proteins of the lysosomes, ER or Golgi itself.
Lysosomes
- contain hydrolytic enzymes which break large molecules into small subunits
- enzymes are only active at an acidic pH of 5.0 in the lysosome
- degrade extracellular and intracellular debris (recycle worn out organelles and destroy bacteria or viruses brought into the cell by fusing with them)
Peroxisomes
- contains oxidative enzymes which use oxygen to remove hydrogen from molecules, breaking them down
- break down fatty acids, alcohol and drugs
- abundant in liver and kidney
This is a by-product of the actions of the oxidative enzymes and is toxic
hydrogen peroxide
Peroxisomes have an enzyme called __________ which breaks down hydrogen peroxide into water and oxygen
catalase
Mitochondria
- cells that need more energy have more MT
- have own DNA -only organelle other than nucleus to have DNA
Cytoskeleton
- non-membrane bound organelle (only ribosomes and cytoskeleton have no phospholipid bilayer surrounding them)
- composed of protein filaments or cytoskeletal filaments
General functions of cytoskeleton
- maintain cell shape
- maintain the position of organelles in the cell
- mediate cell and organelle motility
Cytoskeletal filaments include: (3)
- Microfilaments -made of the protein actin
- Intermediate filaments -many different proteins act as intermediate filaments (intermediate filaments are part of desmosomes)
- Microtubules -made of the protein tubulin
Vesicular transport
- form of transport that uses vesicles to move substances across biological membranes
- endocytosis and exocytosis
Endocytosis
- uptake of material into the cell using vesicles containing material that pinch off from the plasma membrane and enter the cytoplasm of the cell
- 3 types of endocytosis: phagocytosis, pinocytosis, receptor-mediated endocytosis
Exocytosis
- release of material from the cell using vesicles containing material that fuse with the plasma membrane and release their contents into the extracellular fluid
Phagocytosis
- also called cell eating
- uses extensions of the plasma membrane called pseudopodia to surround material being brought up into the cell
- used for bringing large particles into the cell, such as bacteria or cell debris from nearby cells
- process used by white blood cells
Pinocytosis
- also called cell drinking
- plasma membrane simply ‘indents’ below the particles to be brought into the cell (does not use pseudopodia)
- plasma membrane pinches together once it has indented and the vesicle containing particles brought into the cell is called an endocytic vesicle
- nonspecific process -simply brings in extracellular fluid and substances dissolved in that fluid
- used to ingest small molecules, ions and nutrients (cannot bring in large things into the cell such as bacteria or cell debris)
Steps of Phagocytosis
- once activated, the phagocytic cell moves to the material it will ingest.
- Recognition of substance to be ingested
- Attachment of phagocyte to the substance to be ingested
- Pseudopodia reach around substance and come together to form a phagosome inside the phagocytic cell
- Fusion of the phagosome to a lysosome to form phagolysosome
- Destruction of ingested substance by lysosomal enzymes
- Release of end products into the cell or out of the cell by exocytosis
Receptor-mediated Endocytosis
- specific process as it involves receptors which bind specific ligands to be brought into the cell
- involves cytoplasmic protein called clathrin
Process of receptor-mediated Endocytosis
- Binding of ligand to receptor produces conformational change in receptor which recruits, or causes, clathrin to move to the membrane.
- Many receptor-ligand complexes are localized to one area of membrane lined by clathrin, therefore can concentrate the ligand that is taken into the cell.
- The membrane lined by clathrin containing the receptor-ligand complexes indents and a clathrin coated pit is formed (simply the indented membrane with clathrin and receptor-ligand complexes)
- A vesicle pinches off containing the receptor-ligand complexes and is lined by clathrin
- Clathrin is released form the vesicle.
- Vesicle may:
- deposit contents into the lumen of an organelle
- travel across teh cell and fuse with plasma membrane to release contents outside cell
- fuse with organelles called endosomes which then sort contents to the Golgi or lysosomes
Functions of exocytosis
- to secrete specific substances (ie. hormones)
- release waste products
- add components of the membrane, such as lipids and proteins, to the plasma membrane when vesicles fuse with the membrane. This balances portions of plasma membrane removed by endocytosis.
There are transport process or driving forces that do not utilize vesicles to move substances across membranes. What are the three driving forces?
- Chemical driving force
- Electrical driving force
- Electrochemical driving force
Chemical driving force
- there is a chemical driving force when there is a different concentration of a substance on either side of a membrane
- molecules move passively from a high to a low concentration, or ‘down’ the concentration gradient
- as the side of the gradient increases, the rate of transport of the substance increases
- chemical driving is due to the concentration gradient of a substance
Electrical driving force
- any substance that is charged will be affected by the electrical driving force
- the electrical driving force exists due to the membrane potential. Cells in our bodies have a membrane potential
Membrane potential
- a difference in the electrical potential or voltage across a cell membrane
- also called a ‘separation’ of charge across the membrane
- any charged substance experiences attractive or repulsive forces due to the membrane potential. The membrane potential will ‘push or pull’ a charged substance in different directions, depending on the charge on the substance (ie. positive or negative) and the membrane potential
Electrochemical driving force
- the sum of the electrical and chemical driving forces acting on an ion
- remember: neutral substances are not affected by the electrical driving force
- direction that the electrochemical driving force acts depends on the net direction of the electrical and chemical driving forces.
Simple diffusion
- the passive movement of molecules through a biological membrane’s lipid bilayer
- does not require the input of energy
- substances that move by simple diffusion move from a region where they are found in high concentration to a region where they are found in low concentration, or ‘down’ their concentration gradient.
How well a substance crosses a phospholipid bilayer depend on the _________________ and its ______
solubility of the substance in lipid (is it polar or nonpolar) and its size (the smaller the substance, the more easily it can move between the phospholipids in the membrane).
Remember the membrane is a made of phospholipids and has a nonpolar core due to the presence of the nonpolar fatty acid tails of the phospholipids.
polar= water soluble, lipid-insoluble
nonpolar= water-insoluble, soluble in lipids
Which substances move across a phospholipid bilayer by simple diffusion?
- Substances which are small may move across a membrane by simple diffusion, but have to consider their charge (are they polar or nonpolar or do they have a charge (positive or negative, like an ion)?
1. if a substance is small, nonpolar and uncharged= it can cross by simple diffusion.
2. If a substance is polar and uncharged= it may cross by simple diffusion if small enough - If a substance is large, uncharged and polar, it will not cross by simple diffusion (it does not have a charge, but being polar and large will not allow it to cross by simple diffusion)
- Any substance that has a charge (positive or negative), regardless of its size (small or large) cannot cross by simple diffusion. (for example, ions are very small but their positive or negative charge will not allow it them interact with the nonpolar tails of the phospholipids and cross by simple diffusion).
Factors influencing the rate of simple diffusion
- Magnitude of the driving force -the greater the concentration difference of a substance one either side of the membrane, the greater the magnitude of the driving force and the greater the rate of simple diffusion.
- Membrane surface area -how much membrane is available for substances to cross? A large cell has a bigger surface area than a smaller cell, and more molecules of a substance can cross the membrane at one.
- Membrane permeability
The permeability of a membrane to a particular substance depends on the nature of the transported substance as well as the properties of the membrane. It depends on: (4)
- the lipid solubility of the diffusing substance
- nonpolar substances cross the membrane more readily - Size and shape of the diffusing substance
- small and more regularly shaped substances cross the membrane more readily - Temperature
- at higher temperatures substances move around more, which help them diffuse faster across the membrane - Diffusing distance
- this refers to how ‘thick’ the diffusing distance is
- If a substance has to cross more layers of cells, it will diffuse much slower than if that substance had to cross only one layer of cells
- this is an inverse relationship: a smaller diffusing distance results in a faster rate of simple diffusion.
Osmosis
- refers to the net movement of water across a selectively permeable membrane driven by a difference in solute concentrations on the two sides of a membrane.
- water flows from a region of high water concentration to a region of low water concentration. This is the same as saying water flows from a region of low solute concentration to a region of high solute concentration.
How do we change the concentration of water?
By adding a solute
Pure water is water with no solute added
When you add solute, you reduce the ‘concentration’ of water
Water can move across membranes by ________________
simple diffusion
- water molecules are polar but small
- the simple diffusion of water across membranes is limited and finite
Certain tissues have a larger permeability to water, such as the _________
kidneys
This is achieved by the presence of water channels called aquaporins, which water easily moves through.
The use of a protein to cross the cell is mediated transport.
What are the two forms of mediated transport?
- Facilitated diffusion
- Active transport
Facilitated diffusion
- Passive transport: energy is not required in this process as substances move passively down their concentration gradient
- types of proteins involved are carriers or channels
- it is a specific transport process
- carriers are proteins with specific binding sites for the substance to be transported across the membrane
- channels are selective for a specific ion (ie. a sodium ion) or a type of ion (ie. may allow cations only or anions only to pass through)
2 types of facilitated diffusion
- Carrier-mediated facilitated diffusion
- Channel-mediated facilitated diffusion
Carrier-mediated facilitated diffusion
- involves transport proteins called carriers which have a specific binding site for the substance to be transported
- these proteins bind the substance and move it across the plasma membrane, from a region of high concentration to a region of low concentration
- does not require the input of energy, such as ATP
- example: GLUT family of proteins which are carriers that move glucose across the membrane from a region of high concentration to a region of low concentration (glucose is nonpolar and uncharged but it is too large to move across the membrane by simple diffusion)
Channel-mediated facilitated diffusion
- channels may be selective for a specific ion or type of ion that moves through them
- channels do not just allow ions to pass through. For example, aquaporins are water channels that are specific for water molecules
- the direction and magnitude of ion flux through a channel depends on the electrochemical gradient of that ion
- channels exist in an open or closed state and may be gated. Gating refers to the opening (activation) or closing (by deactivation or inactivation) of ion channels. Gating is the process of an ion channel transforming between any of its conducting and non-conducting states.
Channels may be: (3)
- Voltage-gated (changes in voltage cause the channel to open or close)
- Ligand-gating (the binding of a substance or ligand to a binding site on the channel causes it to open or close)
- Mechanically-gated (mechanical stimuli such as swelling or stretching of a cell causes the channel to open or close)
Active transport
- involves transport proteins with specific binding sites for the substance to be transported
- capable of uphill transport, or moving a substance against an electrochemical or concentration gradient from low to high
- often called pumps
- utilize energy to mediate uphill transport
- primary or secondary active transporters obtain energy from different sources
Primary active transport
- use ATP as energy source to drive the transport process
- example: Na+/K+ pump
-At rest, a cell has a high [Na+] outside the cell and high [K+] inside the cell.
-Na+/K+ pump moves 3 Na+ ions out of the cell and 2 K+ ions into the cell for every molecule of ATP hydrolyzed. This pump moves Na+ and K+ ions against their concentration gradients.
-Functions of pump: contributes to establishing and maintaining the membrane potential of the cell and maintains the Na+ and K+ concentration gradients
Secondary active transport
- energy source to drive the transport process: movement of an ion down its electrochemical gradient
- couples movement of an ion down its electrochemical gradient with that of an another substance moving against its concentration gradient
- Example: Na+/glucose cotransporter or Na+/H+ exchanger. In both cases Na+ moving down its electrochemical gradient provides the energy to move H+ or glucose against its electrochemical (H+) or concentration gradient (glucose)
Transport rate for simple diffusion
- Simple diffusion is an unsaturable transport process as it does not involve proteins and binding sites; as you increase the concentration of the substance, you increase the movement of substance across the membrane
Transport rate for mediated transport
- Mediated transport is a saturable transport process as it involves proteins and binding sites; each cell has a limited number of proteins and each protein has a limited number of binding sites for a substance. As the concentration of substance increases, an increased number of binding sites are occupied. The transport rate will plateau, or stop increasing, once all sites are occupied; at this point further increasing the concentration will not further increase the transport rate.
Chemical messengers
- a form of intracellular communication; intracellular -“between cells”
- may be lipid-soluble or lipid-insoluble
- used for the process of signal transduction, which is the sequence of events between the binding of a messenger to a receptor and the production of a cellular response
Properties of Receptors
- receptors have specific binding sites for a specific messenger
- receptors show saturation, in that they have a defined number of binding sites for a messenger (a single receptor may have only 1 or 2 binding sites for a messenger)
- receptors bind different messengers with different affinities. Affinity refers to how strong a receptor and messenger bind; high affinity means they bind very strongly a low concentrations while low affinity means that the interaction between messenger and receptor is weaker and it requires higher concentrations of a messenger to bind. Some receptors bind a particular substance with high affinity while other receptors bind to their substance with low affinity.
- receptors may be found on the plasma membrane or intracellularly, in the cytosol or in the nucleus.
Intracellular receptors
- these receptors are found inside the cell, in the cytoplasm or in the nucleus
- lipid-soluble chemical messengers diffuse across the plasma membrane and bind to intracellular receptors
- example of chemical messengers that bind to intracellular receptors: steroid hormones (hormones derived from cholesterol)
- chemical messengers which bind to intracellular receptors act as transcription factors
Transcription factors
- alter the rate of transcription of mRNA in the nucleus by binding to a response element.
- a response element is a specific sequence of DNA near the beginning of a gene. By binding to the response element, a chemical messenger can alter the rate of transcription of a gene, which alter the rate of translation of the mRNA into a protein (each gene contains the instructions for producing a specific protein)
- transcription factors alter the rate of protein synthesis
Membrane-bound receptors
- chemical messengers that are water-soluble (hydrophilic; lipid-insoluble) cannot diffuse across the hydrophobic core of the plasma membrane; bind to receptors on the extracellular surface of the plasma membrane
- examples include peptide or protein hormones
3 types of membrane-bound receptors
Channel-, enzyme-, or G-protein- linked receptors
First messenger
extracellular chemical messenger that binds to a specific membrane-bound receptor
Second messenger
a substance that enters or is generated in the cytoplasm of a cell following the binding of the first messenger to its receptor
Protein kinase
an enzyme that phosphorylates another protein, or adds phosphate groups to the protein. By adding phosphate groups to a protein, a protein kinase alters the activity of another protein
Receptors that are ligand-gated ion channels
- A membrane-bound receptor
- This receptor (a protein) has a receptor component with binding sites for a chemical messenger and an ion channel component. It is one protein that functions both as a receptor and an ion channel.
- This is a fast process as the receptor and ion channel are a single protein
- The channel in the receptor may eb a calcium channel. Calcium has many roles in the cell
Steps of signal transduction (3)
- a first messenger binds to binding sites on the receptor
- an ion channel in the receptor protein opens
- ions move through the channel. As the ions have a charge, they alter the electrical properties of the cell and produce a response.
Receptors that function as enzymes
- A membrane-bound receptor
- This receptor (a protein) has a receptor component with binding sites for a chemical messenger and intrinsic enzyme activity (intrinsic= within the receptor protein)
- also called receptor tyrosine kinases: the enzyme part of the receptor is a kinase that phosphorylates tyrosine amino acid residues (ie. adds phosphates to tyrosine amino acid residues)
- the tyrosine kinase part of receptor autophosphorylates or phosphorylates tyrosine amino acid residues on the receptor
- the phosphorylated tyrosines (phosphotyrosines) on the receptor act as docking sites for proteins in the cytoplasm of the cell
- once a protein binds to the phosphotyrosines it is activated by phosphorylation, and will bind to other proteins in the cell to eventually produce a response.
G-protein linked receptor
- membrane-bound receptor that binds extracellular chemical messengers
G-proteins
- found at the cytosolic surface of the plasma membrane
- bind guanosine nucleotides (GDP or GTP), and this is why they are called G-proteins
- a protein made of 3 subunits called alpha, beta and gamma
- function as a link between the receptor in the plasma membrane and an effector protein, which is an ion channel or an enzyme
- both the receptor an the effector protein interact with the G-protein
- only the alpha subunit of the G-protein binds to GTP or GDP, not the beta and gamma subunit
Alpha subunit of the G-protein binds the GDP when ______
inactive
Alpha subunit of the G-protein binds the GTP when _______
active
G-protein linked receptors
- Binding of an extracellular first messenger to a membrane-bound receptor causes a conformational change in that receptor, altering the affinity of the alpha subunit of the G-protein for GDP.
- The affinity of the alpha subunit for GDP decreases and the affinity for GTP increases; the alpha subunit releases GDP and binds GTP - The G protein will now dissociate from the receptor and the GTP-bound alpha subunit is activated and separates from the beta and gamma subunits.
- The activated alpha subunit moves to its target protein in the membrane, called the effector protein.
- Effector protein is either an enzyme or an ion channel
- The GTP-bound alpha subunit will alter the activity of this effector protein to produce a response in the cell - The activated alpha subunit hydrolyzes, or breaks down, the GTP to GDP and inorganic phosphate, returning itself to the inactive state in which it is bound to GDP. The alpha subunit recombines with the beta and gamma units, which anchor the alpha in the membrane.
- The G-protein with the 3 subunits (alpha, beta and gamma) then recombines with the receptor
How does binding of a first messenger alter the activity of an effector ion channel? (4)
- Binding of first messenger to receptor causes conformational change in receptor
- Affinity of α-subunit for GTP increases; GDP dissociates, GTP binds
- GTP-bound α-subunit dissociates from β and γ; moves to ion channel
- Ion channel opens or closes (depending on state of channel prior to binding of GTP-bound α-subunit), alters flow of ions across membrane
How does binding of a first messenger alter the activity of an effector enzyme? (5)
- Binding of first messenger to receptor causes conformational change in receptor
- Affinity of α-subunit for GTP increases; GDP dissociates, GTP bind
- GTP-bound α-subunit dissociates from β and γ; moves to enzyme
- There are different types of G-proteins:
- If the G-protein is Gs protein, it stimulates or activates the enzyme;
- If the G-protein is Gi protein, it inhibits the enzyme - Altering the activity of the enzyme alters the production of a second messenger by the enzyme in the cytosol
Steps involved in the production of cAMP (7)
- Binding of a first messenger to a receptor causes a conformational change in the receptor. This increases the affinity of the alpha subunit for GTP; GTP binds after the release of GDP.
- The activated alpha subunit of the Gs protein separates from the beta and gamma subunits and moves to and binds to adenylyl cyclase, activating it.
- Adenylyl cyclase is a membrane-bound enzyme
- A stimulatory G protein of Gs stimulates or activates adenylyl cyclase - The catalytic site of adenylyl cyclase is located on the cytoplasmic surface of the plasma membrane; adenylyl cyclase catalyzes the conversion of cytosolic ATP molecules into cyclic AMP.
- Cyclic AMP acts as a second messenger and diffuses through the cytoplasm.
- cAMP binds to and activates protein kinase A (PKA), which is also called cyclic-AMP-dependent protein kinase.
- PKA requires cAMP to activate it - Activated PKA catalyzes the phosphorylation of proteins in the cell by transferring a phosphate group from ATP to cellular proteins.
- Once these cellular proteins have been phosphorylated, their activity is altered, resulting in a cellular response.
cAMP second messenger system
- most common second messenger system found in the cells in our body
______ may act as a second messenger in cells
Calcium
- Calcium normally found in low concentration in the cytoplasm
- Calcium may enter the cell from the extracellular fluid following the binding of a first messenger to a receptor
- The receptor may be a receptor that is ligand-gated ion channel, in which case the intrinsic ion channel opens and allows calcium to move into the cell. The receptor may be a G-protein linked receptor, which will open a calcium channel in the membrane. With either receptor, calcium enters the cell and its concentration increases in the cytoplasm.
Is the increase in calcium levels in the cytoplasm enough to produce a response in the cell?
The increase in calcium levels in the cytoplasm is not enough to produce a response in the cell; Calcium that has entered the cytoplasm from the ECF will bind to receptors on an organelle called endoplasmic reticulum (the ER may store calcium; it has a high concentration of calcium).
Binding of calcium to receptors on the ER causes calcium to be released from the ER, further increasing levels in the cell; this is called calcium-induced calcium release as calcium entering the cell from the ECF causes its own release form the ER into the cytoplasm
Calcium activates __________, which is a cytosolic protein that is normally found inactive in the cell; ________ requires calcium to activate it.
calmodulin
Activate calmodulin activates a _____________
calmodulin-dependent protein kinase
The protein kinase phosphorylates proteins in the cell, producing a response.
