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Systems Physiology
Cell Signaling
50
Biology
Undergraduate 3
03/04/2006

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Term
True/False: The sex hormone going through the blood are constant
Definition
True
Term
T/F Estrogen can get so low during menstruation that there is none.
Definition
False - There is always some estrogen present.
Term
The most "public" type of communcation involves broadcasting the signal throughout the body by secreting it into the bloodstream, this is the _________ system and relies on the signaling of _________
Definition
Endocrine system; hormones
Term
What system signals neighboring cells? What kinds of signals does it use?
Definition
The paracrine (para = near) system uses local hormones like growth factors, and cytokines (like prostaglandin for local inflammation) and chemicals like nitric oxide
Term
Describe the action and importance of nitric oxide (NO)
Definition
This dissolved gas diffuses readily out of the signal cell and enters neighboring cells. Made from amino acid Arginine. A nerve cell can activate endothelial cells to create NO which diffuses rapidly into smooth muscle cells. The receptor in the muscle cell causes the cell to relax and the blood vessels can relax (dilate) and blood flows freer
Term
How does Viagra work?
Definition
It blocks the degradation of cyclic GMP, which elongates the NO signal (and thus the penis.)
Term
The autocrine system is similar to the paracrine system. What is the major difference?
Definition
In the autocrine system, the cell produces a signal which turns around and acts on the cell itself.
Term
What is "contact dependence" signaling? Give an example
Definition
The cell holds the signaling molecule in its membrane and the signaling cell "kisses" the receptor on the target cell. In embryonic cells, the signal is called "delta" and the receptor is called "notch" and the cells with "delta" become nerve cells.
Term
Describe the signaling of the activation of osteoclasts
Definition
RANKL (the L is for Ligand) is the signal produced by an osteoblast, the receptor on the osteoclast is "RANK" and the signal causes the osteoclast to resorb bone
Term
How critical is the receptor to identify the presence of signals?
Definition
The receptors are just as important as the signals. Males MUST have receptors for testosterone, or they will develop as females (even though they are producing enough testosterone)
Term
Describe acetlycholine, and how it affects different cells in different ways, and what this means
Definition
Acetlycholine is a hormone, a neurotransmitter. It causes heart muscle cells to decrease contraction, causes salivary gland cells to increase secretion of saliva, and causes muscle cells to increase contraction. These different responses are due to different signaling cascades, different cell functions, and different receptors.
Term
What can signals/receptors control?
Definition
Survival, proliferation (division), differentiation
Term
What happens when a cell experiences an absence of any signals?
Definition
Programmed cell death - apoptosis.
Term
Do large, hydrophilic molecules diffuse through the plasma membrane?
Definition
No way! They are too big and hydrophilic.
Term
Do small, hydrophobic molecules diffuse across the plasma membrane?
Definition
Totally. examples: nitric oxide (NO), and steroid hormones
Term
What are steroid hormones?
Definition
They are hydrophobic signal molecules which cross the plasma membrane and activate a receptor protein located either in the cytosol or the nucleus to then either promote or inhibit the transcription of a selected set of genes
Term
Give some examples of steroid hormones
Definition
Estrogen, testosterone, cortisone, progesterone, cortisol, estradiol, thyroid hormones such as thyroxine
Term
How does a steroid hormone control gene expression?
Definition
It enters the cytosol and causes a conformational change to a steroid hormone receptor. The receptor forms a dimer with Retinoid Acid Receptor (RXR), the complex enters the nucleus through nuclear pores and acts as a transcription factor to the DNA.
Term
What are the 3 familes of cell-surface receptor proteins?
Definition
Ion-channel-linked receptors
G-protein-linked receptors
Enzyme-linked receptors
Term
What do all membrane-bound receptors have in common?
Definition
The ligand (the signal) binds to the receptor, and the receptor undergoes a conformational change.
Term
What type of receptor involves the smallest ligands?
Definition
Ion-linked receptors
Term
What happens in ion-linked receptors?
Definition
A small molecule binds to an ion channel, causing a conformational change (the channel opens or closes) and ions rush in or out, which produces and electrical current
Term
Why is Ca++ called the "second messenger"?
Definition
Because the ligand is the first. The Ca++ is the 2nd step in the transduction of the signal.
Term
Give examples of the types of ions which flow through ion channels
Definition
Na+, K+, Ca++, Cl-, i.e. small ions
Term
Ion-channel-linked receptors are characteristic of what system in the body? Where else?
Definition
The nervous system, other electrically excitable cells such as muscle cells
Term
How reactive is Ca++?
Definition
It is very reactive
Term
What is so special about Ca++?
Definition
It is a great 2nd messenger because the concentration of Ca++ in the cytoplasm is about 10^-6 M. It's a poison, so it is either pumped out of the cell, or sequestered in the s.E.R.
Term
What is a good example of a Ca2+ binding protein?
Definition
Calmodulin binds each Ca2+ in series, with a conformational change each time to allow the next Ca++ to bind, there are 4 Ca++ binding spots in all
Term
What are some other good 2nd messengers besides small ions?
Definition
cAMP, GTP, ATP
Term
After the ion-channel-linked receptor is activated, what happens next? Or, what does the 2nd messenger then do?
Definition
The 2nd messenger activates an enzyme Kinase. The Kinase phosphorylates a new enzyme, and it's a whole chain of (Kinase + Pi ----> Kinase + Pi ---> Kinase + Pi
Term
What turns off the chain of Kinase phosphorylation?
Definition
A phosphotase can remove the phosphate group (like "minus Pi"), thus the phosphotase is just as important as the kinase.
Term
What is the largest family of cell-surface receptors?
Definition
G-Protein coupled receptors
Term
What does GTP stand for?
Definition
Guanosine tris-phosphate
Term
What does a G-protein coupled receptor look like?
Definition
A single polypeptide chain threads back and forth across the lipid bilayer 7 times ("seven-pass transmembrane receptor proteins")
Term
What is rhodopsin?
Definition
The light-activated photoreceptor protein in the vertebrate eye. It is a G-protein-coupled-receptor
Term
What are the 3 subunits of a G-protein?
Definition
alpha, beta and gamma. The alpha and gamma are associated with the plasma membrane and the beta is sort of...not. it's associated with the alpha and gamma though
Term
Describe the alpha-subunit of a G-protein in an ACTIVE state and in an INACTIVE state.
Definition
ACTIVE - GTP is bound
INACTIVE - GDP is bound.
Term
What happens when a GPRC is activated?
Definition
A signal (extracellular ligand) binds to the receptor, causes a conformational change, the tail hits the alpha-subunit of the G-protein and a conf. change causes the GDP to dislodge and a GTP to come and bind. The alpha subunit then dissociates from the beta-gamma complex, and they both roam freely, relaying the signal.
Term
What happens to stop a GPRC signal?
Definition
The activated alpha-subunit of the G protein (which has GTP bound) has intrinsic GTP-hydrolyzing activity (GTPase) which makes the GTP->GDP and the alpha subunit reassociates with the beta-gamma complex and the signal is shut off.
Term
Describe the action of Cholera toxin
Definition
It is a bacteria which makes the toxin which inhibits the alpha-subunit to hydrolyze GTP->GDP, which keeps the signal on. Also, free beta-gamma complexes eventually light on an ion channel, and lock it into being always open.
Term
Describe the action of Pertussis toxin
Definition
A bacteria colonizes the lung, and produces this toxin which alters the alpha-subunit and locks it into the GDP state, which permanently turns off the GPRC.
Term
Draw the structure of a phospholipid. What does phosphatidyl inositol look like?
Definition
.
Term
What does a lipase do?
Definition
It cleaves a phospholipid.
Term
What does Phospholipase C do to Phosphatidyl inositol?
Definition
It cleaves the phospholipid at C3, producing diaclyglycerol (two, fatty acids, on a glycerol C-C-C) and inositol tris phosphate (IP3)
Term
Once PLC cleaves at C3, what happens?
Definition
The DAG stays in the membrane, and the IP3 (charged) goes to the sER and finds and ion channel and causes a conformational change which rushes Ca2+ into the cytoplasm. An enzyme in the cytoplasm (Protein Kinase C) binds to the Ca2+ ion, and thus the PKC undergoes a conf. change and is pulled to the membrane by the DAG! Once there, the PKC (a Kinase) starts phosphorylating things and begins a kinase cascade chain
Term
Describe the action of Protein Kinase C
Definition
PKC is located in the cytoplasm, Ca2+ from the sER conformationally changes the PKC. The PKC is then pulled to the plasma membrane by DAG, and then the PKC (a Kinase) starts phosphorylating things and begins a kinase cascade chain
Term
Describe the action of PLA2
Definition
Phospholipase A2 cleaves at C2, which holds the 2nd fatty acid, which is almost always arachidonic acid. The arachidonic acid can be acted on by cycloxygenase and make prostaglandins which can further amplify the signal
Term
Besides producing DAG and IP3, what else does PLC do?
Definition
It can activate another enzyme, adenylate cyclase, which causes:
ATP--> AMP --> cAMP The whole path:
Signal, GPRC, G-protein, alpha-subunit, adenylate cyclase, ATP, AMP, cAMP
Term
How does the 2nd messenger cAMP work?
Definition
It is produced by adenylate cyclase, it then activates Protein Kinase A (PKA) which can start a phosphorylation cascade. cAMP is degraded by a phosphodiesterase (the cAMP is decyclized to AMP)
Term
Signal cascades are usually really fast. When do they slow down?
Definition
When they start to affect gene expression by acting on mitogen activated protein kinases (MAP Kinase)
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