Exam III Flashcards
What type of cellular movement occurs with a concentration gradient?
Passive diffusion
What type of cellular movement occurs against a concentration gradient?
Active transport
What types of proteins are found within the plasma membrane?
Ion channels, transporters, and pumps
What is the main cation found in intracellular fluid?
Potassium (K+)
What is the main cation found in extracellular fluid?
Sodium (Na+)
This process is characterized by random movements powered by a concentration gradient ONLY (high to low) and it occurs until equilibrium is reached
Diffusion
What are some factors that determine the amount of diffusion that is occurring?
A concentration gradient, particle size, and the permeability of the compound in the barrier it is trying to cross
Can lipid-soluble molecules diffuse through a lipid bilayer?
Yes, but it depends on the solubility of the lipid
Can water and other lipid-insoluble compounds diffuse through the lipid bilyaer?
Yes, but they require protein channels/pores to enter
In diffusion there are two different types of channels that allow substances into and out of the cell. What are they?
Voltage-gated channels and ligand-gated channels.
Sodium channels and potassium channels open when the inside of the cell membrane becomes positively charged. What types of gating would this be considered?
Voltage-gating
The binding of a molecule to a channel will result in this type of gating.
Chemical gating
In this type of cellular transport a carrier protein is required. Each carrier protein has a specific affinity for binding a molecule.
Facilitated diffusion
In facilitated diffusion, transport proteins are sometimes called…
Permeases
This term is used when a solute concentration gives half of Vmax.
Km
This is the maximum attainable reaction rate based on the initial enzyme concentration
Vmax
This term refers to the diffusion of water across a semipermeable membrane, but not solutes.
Osmosis
During osmosis, ____allows water into the plasma membrane.
Aquaporins
This is the pressure applied to stop the flow of water to the side of the highest concentration.
Osmotic Pressure
When the osmotic pressure inside and outside of the cell is the same.
Isotonic
This term is used to describe cells that have a higher osmotic pressure inside than outside. Water is moving into the cell, which increases cell volume.
Hypotonic
This term is used to describe cells that have a higher osmotic pressure outside of the cell rather than inside. Water is moving out of the cell, which decreases cell volume.
Hypertonic
What is the term used to describe a scalloping of the cell membrane?
Crenation
Which type of cells are more resilient to changes in osmotic pressure? Animal or Plant?
Plant cells, because they have a cell wall.
What type of cellular transport moves against a concentration gradient, requires ATP, and requires a carrier protein?
Active transport
Movement of ions during cellular transport creates an ion gradient, which powers this type of active transport.
Secondary active transport
What are the two types of secondary active transport?
Co-transport (molecules are moving in the same direction) and Counter transport (molecules are moving in different directions)
What are the classes of primary active transport pumps?
P-class, F-class, V-class, and ABC-class
What are the two subunit carrier proteins in the sodium-potassium pump?
Alpha and beta
Where does ATPase activity occur within the larger alpha protein in the sodium-potassium pump?
Inside near Na+ binding sites
How many binding sites for sodium and potassium does the larger alpha protein in the sodium potassium pump have?
3 binding sites for sodium and 2 binding sites for potassium
What occurs at the sodium-potassium pump?
2 K+ bind outside and 3 Na+ bind inside, ATPase becomes active, splitting ATP into ADP and Pi. Energy is then released causing a conformation change in the carrier protein. Finally Na+ is pumped to the outside and K+ is brought inside the cell.
Highly active cells (nerves) may devote____% of cell’s energy to the sodium-potassium pump!!
60-70%
What is an important feature of the sodium-potassium pump?
To control cell volume
What would happen to a cell if it didn’t have the sodium-potassium pump?
The cell would swell until it bursts
Swelling of a cell for any reason activates what?
The sodium-potassium pump
How many calcium pumps are allotted to each cell?
Two. One located in the cell membrane and pumps Ca out of the cell. Another pumps Ca into the endoplasmic reticulum or mitochondria
What do both of the Ca pumps of cells act as?
ATPases
What is another name for Hydrogen pumps?
Proton pumps
Where are hydrogen pumps located?
Parietal cells of gastric glands in the stomach and renal tubules.
What do hydrogen pumps do in the stomach?
Secretes H+ that can combine with secreted Cl- to form HCl in the stomach
What do hydrogen pumps do in the renal tubules?
Large amounts of H+ are secreted from the blood into the urine. It also has a buffering function
What are symporters associated with?
Co-transport, which is a type of secondary active transport
What are antiporters associated with?
Counter-transport, which is a type of secondary active transport
What types of things does Co-transport or symporters move?
Glucose and amino acids
What types of things does Counter-transport or antiporters move?
Calcium and hydrogen
What is secondary active transport driven by?
An ion concentration gradient, not by ATP. Transporters do not have ATPase activity
They are transport molecules in the same direction across the plasma membrane. An example is the sodium-glucose transporter
Symporters
With symporters, how are the molecules being transported?
Molecule 1 is moved with the concentration gradient, while molecule 2 is actively transported against the concentration gradient. Both molecules are entering the cell together and in the same direction.
They are transport molecules in the opposite direction across the plasma membrane.
Antiporters
With antiporters how are the molecules being transported?
Molecule 1 is moved with the concentration gradient into the cell. Molecule 2 is actively transported against the concentration gradient out of the cell. Molecules are moving in opposite directions, one into the cell and the other out of the cell
How does glucose transport generally occur?
Facilitated diffusion and secondary active transport
What is the transport protein used in the facilitated diffusion of glucose?
GLUT. Some can be insulin-sensitive while others can be insulin-insensitive
What is the transport protein used in the active transport of glucose?
SGLT, which is insulin-insensitive
When is active transport of glucose used?
Where the glucose concentration within a cell is higher than outside of the cell
What is the process of glucose absorption in the small intestine?
Sodium binds to SGLT-1, glucose binds to SGLT-1, both are then transported in the enterocyte (symport/co-transport), and energy is then derived from the eletrochemical gradient of sodium created by the sodium-potassium ATPase in the basolateral membrane
It is expressed in your liver, kidneys, pancreas, and intestines. It also removes excess glucose from the blood or intestinal lumen
GLUT2
What is the rate of facilitated glucose transport based on?
The glucose available and the number of GLUT proteins available
It is a molecule that aids in the facilitated transport of glucose and is found in most tissues. It uses GLUT 1, 2, and 3, requires a concentration gradient of glucose and is found in RBC, WBC, liver, and brain cells
Insulin-insensitive transporters
How is glucose transported after a sugar-rich meal?
Through active transport and facilitated diffusion. SGLT1 becomes saturated, GLUT 2 is found in the brush border membrane and absorbs glucose by facilitated diffusion. The more carbs that are eate the more GLUT2 that is found in the apical membrane.
What are some factors that increase intestinal apical GLUT2?
Fructose, glucose, surcrose, artificial sweeteners, high carb diet, etc.
What decreases the concentrations of intestinal apical GLUT2?
Certain polyphenols (quercetin)
They are involved in the facilitated diffusion of glucose and are found in skeletal muscle, adipose tissue, and intestinal epithelia. It uses GLUT 4 and 2
Insulin-sensitive transporters
It is a peptide hormone that is secreted from the beta cells of the islets of langerhans in the pancreas. It is secreted in response to glucose and amino acids in the blood.
Insulin
What are some examples of insulinotropic amino acids?
Leucine, phenylalanine, tyrosine, and arginine
What is insulin inhibited by?
Epinephrine
It is located in pancreatic beta cells and is in charge of releasing insulin into the blood. They have a low affinity for glucose.
GLUT2
What is the action of insulin on interstitial GLUT2?
It pulls GLUT2 from the brush border and basolateral membranes to decrease glucose absorption
What is the action of insulin in muscle cells?
- Insulin receptor substrate 1 (IRS-1) is recruited.
- GLUT4 is made and moved to the plasma membrane.
- Glucose enters the muscle and adipocytes
- Insulin levels decrease, GLUT4 is removed
- Vesicles form endosomes (for reuse and recycling)
This disease is characterized by the destruction of beta cells within the pancreas resulting in insulin no longer being released. This is treated with exogenous insulin
Type I diabetes
This disease is characterized by an insulin resistance or a failure of cells to listen to insulin. This can be reversed with diet and exercise
Type II diabetes
What happens when insulin bind to an insulin resistant muscle cell?
C-reactive protein (CRP) abnormally phosphorylates IRS-1 (on 2 serine residues), causing it not to signal properly
What type of diabetes is characterized by an insulin-resistance?
Type II
Most drugs must be transported to the ___ ___ in order to work.
Target tissue
What are the two primary kinds of drugs?
SLCs and ABCs
What body system do the vast majority of drugs use to move through the body?
Circulatory system
They are carriers that can move both xenobiotic and non-xenobiotic drugs. Genetic variations in these transporters make drugs interact with individuals very differently
Solute Carriers (SLCs)
They are carriers that use primary active transport to move drugs into the system. They can be produced by cells in response to drug treatments, which can result in resistance.
ATP-binding cassette transporters (ABCs)
What is the directionality of transport for SLCs?
Mostly transports into the cells
What is the directionality of transport for ABCs?
Mostly transports out of the cells
What is the most well understood ABC transporter and what is it typically involved with?
ABC1 and it is involved in multidrug resistance
This molecule becomes upregulated when exposed to cell death inducing chemicals/drugs. This allows surviving cells to more effectively pump out drugs in the future. Its upregulation can also interfere with other substrates it transports under normal conditions
ABC1
What are the mechanisms being developed to stop multi-drug resistance?
- Engagement (including an additional molecule that binds to a transporter preventing it from exporting the drug molecules.
- Evasion (creating a drug that is no longer recognized by the transporter).
- Exploitation (hijacking the transporters to do what you want to happen with a drug or tricking the cell into breaking down the transporters)
In general, how does cell signalling occur?
A chemical messenger released from one cell binds to a receptor of another cell causing a series of reactions that amplify the message in order to produce the desired effect
They are intracellular signalling proteins that bind to GTP.
G proteins
What are the two subgroups of G-proteins?
Heterotrimeric G proteins and Ras superfamily
What are the three subunits of heterotrimeric G proteins?
A large alpha subunit and two smaller beta and gamma subunits
What are the functions of the alpha, beta, and gamma subunits of G-protein?
Alpha subunit binds to GDP/GTP and when dissociated, interact with certain enzymes. The beta and gamma subunits are inactive when all three subunits are bound
Describe the steps of Heterotrimeric G-protein signalling.
- A ligand binds to G-protein coupled receptor (first messenger)
- G protein activates and regulates an enzyme
- Second messengers amplify the signal
- Serine and threonine are phosphorylated. This phosphorylation changes the biological response
They have 7 transmembrane helices, an extracellular domain, which is the binding site for ligands, and an intracellular domain, which interacts with G-proteins
G-protein coupled receptors
Where have most of the G protein coupled receptors been identified?
In the brain (90% of them)
What is the mechanism for G protein signaling?
- Ligand binding to the G protein coupled receptor causes a conformational change to interact with the G protein.
- G alpha releases GDP, binds GTP, and activates the G protein.
- Galpha then dissociates from the other subunits.
- G protein then activates adenyl cyclase, converting ATP to cAMP and Pi.
What type of molecule is cAMP?
A second molecule messenger
What are some examples of second messenger enzymes?
Adenyl cyclase and phospholipase C
This molecule binds regulatory (R) subunits of protein kinase A releasing catalytic (C) subunits
cAMP
What does phosphorylation do to an enzyme?
It may turn an enzyme on or off
It prevents adenyl cyclase from producing cAMP, preventing enzymes from being phosphorylated
Galphai
Galphas ____ adenyl cyclase. Galphai____ adenyl cyclase.
Activates, inhibits
It converts cAMP to 5’-AMP, inactivating it, and keeping levels low
Phosphodiesterase
What are the steps in phospholipase C activation?
- Hormone or NT binds to a receptor
- Galphaq activates phospholipase C, which then digests IP3 group from PI leaving a DAG.
- IP3 then releases calcium from the ER.
- Calcium and diglyceride then activate protein kinase C (phosphorylating enzyme)
What are ras G proteins?
They are the same as the alpha subunit, but it is not associated with any other subunit. It doesn’t regulate membrane-bound enzymes or produce second messengers.
Why are ras G proteins important?
They play a role in the activation of gene transcription and are important for the regulation of cell proliferation.
What is the signaling mechanism for Ras G?
- Hormone/growth factor binds to a receptor.
- SH2-containing protiens, Ras-specific guanine exchange factor (GEF), and Ras bind to a complex.
- Ras activates
- Raf activates
- MEK activates and phosphorylates MAPK (ERK), which then stimulates gene transcription
- Hydrolysis of GTP terminates this process.
How is the concentration of calcium regulated?
When the levels are high cells produce more calcium binding proteins. CALMODULIN.
Where are taste cells located?
Mouth and the GI tract
These taste cells are the least well characterized. They possibly have to do with salty tastes.
Type I
These taste cells are the most well studied, express G protein-coupled receptors, and can bind sugars (sweet), toxins (bitter), and amino acids (umami).
Type II
These taste cells are thought to be the targets for acids detecting sour tastes.
Type III
What is the G protein in taste cells?
alpha-gustducin
What are some examples of signaling molecules?
Growth factors, cytokines, peptide hormones
What are catalytic/enzymatic receptors?
They are single chain transmembrane proteins.
How is signaling carried out at catalytic/enzymatic receptors?
Signaling occurs through phosphorylation of tyrosine residues. This is regulated by tyrosine kinases and tyrosine phosphatases
What are receptors with tyrosine kinase activity used by?
Growth factors and peptide hormones
What is the structure of receptors with tyrosine kinase activity?
2+ single transmembrane proteins associated together. Each chain has 3 domains (N-terminal=ligand binding domain, Alpha-helical domain across the lipid bilayer, and the effector domain that contains enzymes with tyrosine kinase activity)
What is the mechanism of receptors with tyrosine kinase activity?
- Ligand binding and tyrosine kinase domains activate
- Tyrosines are phosphorylated
- Phosphotyrosines recruit intracellular adaptor proteins
Is Ras an adaptor protein?
Yes
It is a small GTP-binding protein that binds to SH2-containing adaptor protein that binds to phosphotyrosines. It activates serine/threonine phosphorylation and induces the transcription of genes for growth and differentiation.
Ras
What is STAT?
Signal transducers and activators of transcription. It induces transcrition.
Is STAT and adaptor protein?
Yes
What is the mechanism of the phosphatidylinositol 3 (PI3) kinase pathway?
- Phosphotyrosines form
- PI3 kinase binds to phosphotyrosines and activates
- PI3 then phosphorylates inositol phospholipids
- Akt (protein kinase B) is then phosphorylated by PIP3
- Akt phosphorylates Bad, inactivating it and preventing apoptosis.
Do receptors have their own tyrosine kinase activity?
No
What is the insulin signaling mechanism?
- Insulin binds,
- Insulin receptor forms phosphotyrosines
- Insulin receptor substrate (IRS) proteins are recruited to the receptor and phosphorylated.
What are the the types of insulin receptor substrates (IRS)
IRS-1, IRS-2, IRS-3, and IRS-4
What are the most widely expressed IRSs?
IRS-1 and IRS-2
These molecules use intracellular receptors, not membrane bound receptors. The active receptor/ligand complex can bind DNA and regulate transcription
Steroids
What are the types of steroid signaling?
Classical signaling (nuclear-initiated steroid signaling) and Rapid signaling (Membrane-initiated steroid signaling)
What are the two types of steroid receptors?
Type I (sex hormone, glucocorticoid, and mineralcorticoid receptors) Type II (vitamin A, vitamin D and thyroid hormone receptors)
What is the precursor for steroids?
Cholesterol
What are some examples of sex hormones and corticosteroids?
Sex hormones: androgens, estrogen, and progestagens
Corticosteroids: glucocorticoids and mineralcorticoids
Where is the precursor of vitamin D made?
In the liver
What is the final product, active form, of vitamin D known as?
Calcitriol
What is the intracellular receptor structure for steroids within NISS?
Domain 1: ligand binding domain (C terminal)
Domain 2: DNA binding domain (contains zinc fingers)
Domain 3: Gene regulatory domain (N terminal)
What steroid receptors are located in the cytoplasm?
Glucocorticoids and androgens
What steroid receptors are located in the nucleus?
Estrogen, progesterone, vitamin A, vitamin D, and thyroid
What is the mechanism of type 1 NISS?
- Activated receptor ligand complex associates with coregulator protein
- Complex binds to hormone response element through zinc fingers
- Transcription begins
What is the mechanism of type II NISS?
- Unoccupied receptors in the nucleus are bound with corepressor proteins
- Ligand binds to a receptor
- Corepressor is released and coactivator is recruited
- Transcription begins
Each hormone has its own ____ _____ ____ in specifically targeted areas
Hormone response element (HRE)
It is a type of signaling that works rapidly, modifies existing proteins, and may activate kinases that phosphorylate coactivators in NISS.
Membrane-initiated steroid signaling (MISS)?
Where are the membrane receptors located in membane-initiated steroid signaling?
In the calveolae tethered to the plasma membrane by proteins. They can be associated to outer or inner membrane
This is the period of the cell cycle between nuclear division, includes cell growth and DNA synthesis
Interphase
Division of genetic info
Mitosis
Division of cytoplasm
Cytokinesis
During this phase of the cell cycle RNA and protein synthesis are occuring. Replication of organelles and intracellular structures occur and it is the most variable of all cells.
G1 phase
This phase of the cell cycle is a specialized resting state where cells in G1 are not replicating DNA
G0 phase
This phase of the cell cycle is characterized by DNA replication. Chromatin is unwound, DNA is replicated and rewound into chromosomes.
S phase
This phase is the gap of time between the end of S phase and mitosis. Synthesis of RNA and protein occurs here and acts as a checkpoint to ensure nuclear integrity and fix issues
G2 phase
Mitosis contains what 5 phases?
Prophase, prometaphase, metaphase, anaphase, and telophase
During this mitotic phase duplicated chromatin condenses into chromatid, cytoplasmic microtubules form a mitotic spindle at the nuclear surface, and the nucleolus dissapears.
Prophase
Two chromatids are connected by…
A centromere and kinetochore
During this mitotic phase the nuclear envelope disappears and the microtubules that make up the mitotic spindle attach to the kinetochore.
Prometaphase
During this mitotic phase the chromatids align in the middle of the mitotic spindle.
Metaphase
During this mitotic phase polar microtubules elongate and microtubule-kinetochores shorten, causing separation of centromeres. The chromatids then migrate towards the poles of the cell.
Anaphase
During this mitotic phase there is kinetochore microtubule disassembly, dissociation of mitotic spindle, reforming of the nuclear envelope, and decondensation of the chromatids back to chromatin.
Telophase
During this process, actin microfilaments are synthesized to form a contractile ring, contraction of the causes a cleavage furrow to form, the furrow deepens until the edges meet and the 2 daughter cells are formed.
Cytokinesis
This term is used to describe cells who are temporarily in G0 phase.
Quiescence
This term is used to describe cells who are permanently in G0 phase.
Senescence
What two molecules work together to regulate certain phases of the cell cycle?
Cyclins and Cyclin-dependent kinases (CDKs)
These are small proteins that regulate certain phases of the cell cycle. Their concentrations vary throughout the cell cycle due to synthesis and degradation.
Cyclins
These are enzymes present in constant concentrations and also help to regulate the cell cycle. Their activity depends on the cyclin concentration.
Cyclin-dependent kinases (CDKs)
It is a tumor suppressor protein that keeps the cell in G1 by binding factors E2F and DP1/2.
RB protein
It is a tumor suppressor protein that is activated by DNA damage. It stimulates the synthesis of p21 to stop the cell cycle for repair. If the damage cannot be fixed it induces apoptosis.
p53
It controls entry into mitosis, contains inhibitory phosphotyrosines and is a G2 checkpoint regulator.
CDK1
It catalyzes the removal of phosphatases and activation of CDK1. It is a G2 checkpoint regulator.
cdc25c phosphatase
What amino acids is phosphorylation typically associated with?
Serine and Threonine
What does UVB allow your body to produce?
Vitamin D
In the majority of cancers there is a mutation in what protein?
p53
