Biochem EX1 - Signal Transduction Flashcards
What are the difficulties in transducing a signal outside the cell into a cellular response inside the cell?
The cell membrane is impermeable to all but the most simple molecules.
What is a ligand? What is the property of ligands that accounts for the two major classifications of signal transduction?
A ligand is a molecule that binds to a receptor. if it cannot penetrate the cell it binds to a receptor outside of the cell. If it can then it is to an intracellular receptor.
The three histamine receptors (H1, H2, and H3) all bind histamine, but what are the differences in their response to histamine?
H1 - binds to the brain, smooth muscle and endothelium (blood vessels). Binding produces nasal and sinus secretions.
H2 - binds to the brain, cardiac muscles, stomach. binding produces gastric secretions.
H3- binds to the brain, other neurons
Ciproxifan is a potent and specific histamine H3 receptor antagonist. Would it be expected that ciproxifan would alleviate allergy symptoms or suppress gastric acidity? Why?
Ciproxifan would reduce the affinity of the H3 receptor for histidine. H3 has no allergenic or gastric response, so it must have some other neurological effect. H3 affects only the brain and other neurons. H1 would alleviate allergy symptoms and H2 would suppress gastric acidity.
What are three major types of molecular switches for intracellular signaling (hint-the three involve nucleotides in some way), and how is the action of each reversed?
GTP/GDP exchange (reversed by hydrolysis which harms the enzyme)
Kinase (adds a phosphate group) (reversed by phosphatases)
Cyclase (reversed by phosphodiesterase (which breaks a phosphate bond))
Describe the effect of cholera toxin on signal transduction. Begin with how the toxin enters the cell, and end with what the physiological consequences are. Hint-Figures 21-16, 42-5, and 40-19 will help, in that order.
GPCR signals for GTP (a GDP-GTP exchange turns on the first step). We have the expected hydrolysis of GTP to GDP. Now we have the vibrio cholera which makes a cholera toxin which gets into the cell on a normal cell constituent (Ganglioside GM1, a sphingolipid). Whenever one has a toxin, bacteria, or any pathogen it gets into cells by riding in on a normal cell surface component. The Ganglioside GM1 is found on the stomach cells. Once the cholera toxin is inside it breaks the GTPase (the hydrolysis activity is a GTPase activity. Now the cyclase is locked on and instead of having the right amount of cyclic AMP there is a lot of cAMP inside the cell which keeps the kinase turned on and that causes a lot of regulation (at the chloride channel) and a lot of chloride and a lot of water (which leaves by diarrhea causing dehydration). After several hours the dehydration causes death.
What molecule that is a precursor for a lipid involved in signal mediation of inflammation, blood clotting, control of vascular one, pain, and fever is released from membranes by a phospholipase?
Arachidonic acid is cleaved which is a precursor for eicosanoids.
Around 10% of women face depression during pregnancy. Many of these are treated with selective serotonin reuptake inhibitors (SSRIs) which increase the amount of serotonin available to bind to receptors in synapses. Studies of young fruit flies, ice, and humans born to mothers who took SSRIs may show subtle differences such as an aversion to exploring unfamiliar places and heightened aggression compared to those born to unexposed mothers. Remembering that none of these young ever themselves took SSRIs, how do you account for this different long-lasting effect, an effect that is not observed in the mothers while the mothers are taking SSRIs?
A. SSRIs do not cross the placental barrier.
B. Youth of the ages studied are not susceptible to depression, while they are prone to signs of anxiety and aggression.
C. Serotonin has an important role in the developing brain, and a different pattern of where it is released during development, than it does during adulthood.
D. Children have a higher surface area to mass ratio than adults.
E. Serotonin is converted to 5-hydroxytryptamine (5-HT) in infants and small children, and this activity ceases during adolescence.
C. Serotonin has an important role in the developing brain, and a different pattern of where it is released during development, than it does during adulthood.
You want to develop a drug for the elderly or patients suffering from neurodegenerative diseases who might desire a higher level of alertness. You know that antihistamines cause drowsiness, so you decide to try to work to increase the histamine signal transduction pathway for your alertness medication. To achieve the fewest side-effects you would most likely start with a drug specific for
A. H1 receptors
B. H2 receptors
C. H3 receptors
D. histamine receptors
E. antihistamine receptors
C. H3 receptors
There is a whole cascade of events that end with the cellular action in response to the signal, but begin with the detection of signal by a cell. A fortunate consequence of this is that there can be more than one step along the way that can be down-regulated in order to achieve a therapeutic effect, i.e. there are multiple drug targets. Inhibiting stomach acid secretion is a way to reduce heartburn, and a number of formerly prescription drugs are now OTCs. There are television advertisements of Prilosec(omeprazole), which is an H,K-ATPase inhibitor that blocks the action of the cellular pump that acidifies the stomach. There are also television advertisements for which of the following drugs that inhibits the receptor that initiates the cascade that activates H,K-ATPase, and thereby also blocks the pumping of acid by interfering upstream of the cellular pump itself?
A. Zantac (ranitidine)
B. Benadryl (diphenhydramine)
C. Herceptin (trastuzumab)
D. aspirin
E. Toprol XL or Lopressor (metoprolol)
A. Zantac (ranitidine)
