Bio 113 Midterm #3 Chapters 7-11 Integrating and Review Questions

Name two proteins covalently modulated by PKA. Support your answer with data.

phosphoylase kinase and glycogen synthase. see effects in figure 7.12

Sketch a G protein in the active and inactive stages, and label its parts.

inactive: alpha + GDP, beta, gammaalpha + GTP, beta, gammaalpha + GTP ----- beta, gammaalpha + GDP ----- beta, gammainactive: alpha + GDP, beta, gamma

In Figures 9.5 - 9.7, notice that the depolarization disappears and the cell returns to the resting membrane potential. Speculate how cells reset their membrane potentials.

through repolarization (K+ channels opening to repolarize the cell)

Look at the two electron micrographs of muscle cells in Figure 9.16. Can you determine which of the pencil-like proteins in Figure 9.16C are responsible for the light bands of the sarcomere seen in Figures 9.14B and 9.16B? Which proteins produce the dark bands of the sarcomere? Where in Figure 9.16B was the cell cut to produce the view in Figure 9.16C?

. From the 2D images in Figure 9.16, you can see that sarcomeres are composed of two major protein types, dark and light rods. The thicker dark rods form the central dark band of the sarcomere, whereas the lighter protein rods form the two light bands on either side of the dark band in the middle. The cross section in Figure 9.16C was formed by slicing the sarcomere where the dark and light protein rods overlap.

Summarize the three waves of communication through a neuron that will stimulate a muscle.

1) receive a chemical message; 2) produce an electrical current that causes an action potential to move down the axon; 3) produce a new chemical message to tell your muscles to contract

Define a covalent bond, and explain how it is a source of potential energy. Why does the conversion of ATP to ADP in result in negative values for ΔG and ΔH, but a positive value for ΔS? Because every covalent bond is composed of two electrons, do you think that all covalent bonds contain the same amount of energy?

A covalent bond is when two atoms share a pair of electrons. Potential energy is in the covalent bond because energy is required to form covalent bonds and energy is released when they are broken. ATP -> ADP releases energy so the product (ADP) has less potential energy to do work (G) with one less covalent bond, therefore the change (Δ) in G is negative. There are several reasons why different covalent bonds have different amounts of stored energy, but one contributory factor is the difference in electronegativity between the atoms being bonded.

Describe what a kinase does and the protein that performs the opposite function.

A kinase are enzymes that catalyze phosphorylation of proteins (the reaction of attaching a phosphate to covalently modulate its shape and function) with the consumption of ATPA phophatase are enzymes that break covalent bond holding the phosphate in place. Protein phosphates have the opposite functions of kinase and they remove the phosphate group from phosphoproteins by hydrolyzing phosphoric acid monoesters into a phosphate group and a molecule with a free hydroxyl group (28,29)

Be able to explain which neurons in Figure 9.24A were stimulated and which ones were measured to produce the data in Figure 9.24B. Interpret each of the three parts of Figure 9.24B. Describe the stimulus that Kandel and his colleagues gave to a neuron and what they measured.

A, This group of neurons includes motor neurons (red) and sensory neurons (blue). Neurons can be stimulated (S) and measured (M) by one electrode. In the first panel of Figure 9.24B, the investigators stimulated neuron L7 about 20 times in rapid succession and measured the gill's retraction in response. In the middle panel, Kandel and his collaborators stimulated the sensory neuron LE and then measured the action potential in motor neuron L7 communicating with the gill muscle in response to the information passed from LE to L7. For the third panel, the investigators stimulated LE many times, and measured the response in L7 and the retraction of the gill in response to muscle activation by L7. Kandel numbered all the neurons in a cluster located within the body of Aplysia; those on the left side started with the letter L. By stimulating and measuring circuitry in a single pipet, Kandel could stimulate any neuron individually and measure the action potential of the same neuron or a different neuron using an second electrode (Figure 9.24B). Kandel also measured the contraction of the muscle connected to the gill using an instrument not shown in Figure 9.24.

Describe an action potential. What determines whether a particular stimulus will lead to a full action potential or not?

Action potential is a moving wave of electrical current traveling one direction down an axon. The magnitude of the action potential exceeded the initial stimulating voltage (application of +20 mV) because once threshold was reached in a local area, all of the neighboring voltage-gated sodium channels opened and the membrane potential was made less negative, causing more voltage-gated sodium channels to open. As with any form of diffusion, intracellular sodium ions spread to more voltage-gated sodium channels, and localized depolarization reaches threshold again but in a new area. This process produces a full action potential that will spread the entire length of the neuron. The propagation of an action potential is easy to see in an animation to the left.

Explain why an action potential only moves in one direction along an axon. Be sure to address both the initiation of the moving action potential and the repolarization of the neuron. Address both the immediate repolarization and the slower reset of ion concentration gradients.

Action potentials only move in one direction because after voltage-gated sodium channels open, the influx of Na+ causes depolarization. The Na+ channels then close and K+ channels open causing the cell to repolarize. The Na+/K+ pump resets the ion concentration gradient.

Distinguish between covalent and allosteric modulation. Be able to give a specific example of each.

Allosteric Modulation: any molecule or element that that binds non-covalently to a protein and alters the protein's shape and function. ex. agonists Covalent Modulation: attach via covalent bonds to change the protein's shape and function ex. phosphorylation

Study Figure 9.26, and determine which component of short-term memory is responsible for initiating long-term memory. If CREB-1 is functional only when it forms a homodimer, what is the role of CREB-2?

Although cAMP is small enough to diffuse faster than PKA, phosphorylation by PKA is the molecular event that initiates the conversion of short-term memory into long-term memory. One key aspect of long-term memory formation is that the input stimulus must be repeated, and this repetition leads to increased cAMP and consequently increased amounts of activated PKA. Activated PKA not only phosphorylates proteins involved in exocytosis at the nearby synapse, and local Ca2+ ion channels, PKA also diffuses and covalently modulates another kinase called MAPK (pronounced map-kay). Activated MAPK and PKA can diffuse into the nucleus and phosphorylate the regulatory protein CREB-2 and the transcription factor CREB-1. {Connections: Transcription factors were first seen in Section 2.2.} Prior to being phosphorylated, CREB-2 was bound to CREB-1, which prevented CREB-1 from forming an activated homodimer. In other words, CREB-2 inhibits CREB-1 from becoming an activated transcription factor. Phosphorylation of CREB-1 and CREB-2 produces opposite effects on these two nuclear proteins that have similar names but different functions. CREB-2 acts as a threshold detector that ensures the learning stimulus is of sufficient magnitude to overcome its inhibitory capacity. If CREB-2 is not phosphorylated sufficiently (threshold level) due to a weak input signal, then CREB-1 is prevented from escalating the memory into long-term storage.

Using PEDs such as caffeine and other stimulants is common in schools and universities. Are "study drugs" analogous to the use of PEDs in athletics, and therefore should they be considered? Explain your answer.

Although society bans PEDs from sports, drug use in other areas is condoned. Alcohol, tobacco, caffeine, and cocaine are tolerated to different degrees by different segments of society. Health concerns seem to fade away with prescription drugs for energetic children or PEDs by students cramming for finals. Should we apply the same health and fairness standards to drug use outside of athletics?

Does epinephrine modulate its receptor allosterically or covalently? Support your answer with data.

Although there are other forms of covalent modulation, the most common is phosphorylation. Epinephrine is not able to phosphorylate its receptor, so it binds weakly instead which means it is allosteric modulation. The only data presented here is the absence of a phosphorylated receptor protein. Allosteric modulation requires a phosphatase and covalent modulation requires a kinase.

Describe the relationships between primary, secondary, tertiary, and quaternary protein structure. Be able to draw examples of each.

As the side chains begin to interact with each other and water within the cytoplasm, the snakelike proteins begin to bend and fold to maximize the stability of the large molecule. Hydrophobic amino acids tend to accumulate in "oily pockets" that exclude water and hydrophilic amino acids. With this first layer of folding, some characteristic shapes become apparent and are called secondary structures (Figure 7.1B). Spiral alpha helices and zigzagging beta strands form as a result of weak H-bonds between the universal backbones of amino acids aligned in just the right pattern due to the chemical properties of their side chains. Every different protein has its own combination of alpha helices and beta strands as determined by the protein's primary structure. You need to understand proteins in order to understand the function of cells. Protein structure determines its function, which in turn determines the function of every cell on earth. After the secondary structures self-assemble in a newly produced protein, the amino acids continue to wiggle inside a cell to further stabilize the protein's overall structure. New folds, hydrophobic interactions, as well as ionic and hydrogen bonds will form, producing the tertiary structure, which is the overall three-dimensional shape of the protein. If a protein assembles with two or more proteins, then the collection of proteins accumulates quaternary structure, which is the result of the individual proteins interacting based on their already established tertiary structure. Every protein contains primary, secondary, and tertiary structure, and some will form quaternary structure as you will see in Section 7.2.

Refresh your memory of calcium's role in exocytosis by looking at Figure 9.13 and skimming the associated text in Section 9.1. Were calcium channels in Figure 9.26 activated or inhibited when they were phosphorylated by PKA to enhance exocytosis and produce short-term memory? If short-term memory does not persist, what counteracting enzyme must be present to undo the covalent modulation of calcium channels?

As you learned in Section 9.1, Ca2+ is required for secretion of neurotransmitters. When PKA is allosterically modulated by cAMP, PKA covalently modulates calcium channels, which causes the channels to remain open longer than normal. The longer channels are open, the more calcium floods the neuron's terminus, which increases the rate and amount of neurotransmitter release. Similarly, PKA directly stimulates the vesicle proteins involved in exocytosis, which further enhances neurotransmitter secretion. Short-term memory can only persist as long as PKA is activated and the covalent phosphates added by PKA remain intact. You know from your study of signal transduction pathways that each pathway has a mechanism for stopping the signal, and serotonin binding is no exception.

In Figure 7.10, does the G protein α subunit activate adenylyl cyclase directly? Speculate why adding the β/γ complex would result in more cAMP if β/γ do not interact with the cyclase.

Based on the data in Figure 7.10, it appears that the α subunit activated adenylyl cyclase, but not much. However, in the presence of the β/γ complex, the α subunit activated many more adenylyl cyclases. Although the experiment does not test this hypothesis directly, it seems reasonable that the addition of β/γ complex enabled deactivated α subunits to become reassembled with β/γ, and then reactivated by epinephrine receptors with bound epinephrine. The newly ractivated G protein would eject the old GDP, and add a new GTP to further activate adynylyl cyclase, as shown in Figure 7.10.

Is epinephrine the trigger for glucose release from liver? Support your answer with data from Figure 7.6. What is the importance of having p < 0.05 in this figure? Review Bio-Math Exploration 0.1 to refresh your memory of p-values.

Based on the data in Figure 7.6 that used an isolated fish liver, epinephrine is sufficient to trigger a release of glucose. Only experimentally-added epinephrine was needed to stimulate glucose secretion, although another molecule might also be able to stimulate glucose release. Therefore, epinephrine was necessary and sufficient to trigger glucose release from the liver. Epinephrine and its two antagonists compete to bind to the receptor through weak chemical bonds, which means the ligands will wiggle off the receptor periodically. Antagonist 2 was more effective than antagonist 1, but the data do not indicate whether the blocking effects of the two antagonists were significantly different from each other or not. With the p-value being less than 0.05, you can reject the null hypothesis that the two values (epinephrine with and without antagonist) would be equal. {Connections: p-values were first explored in BME 0.1.} Therefore, you can conclude that the amounts of glucose secreted +/- antagonist are significantly different.

Watch the neuron terminus calcium movie associated with Figure 9.12 that shows the influx of Ca2+ in a nerve terminus. Focus on the earliest sites of Ca2+ rise. Do you think the voltage-gated Ca2+ channels are located in only a small region and the Ca2+ diffuses in the cytoplasm, or do you think the voltage-gated calcium channels are evenly distributed on the terminal plasma membrane? You may need to run the movie back and forth a few times to see your answer.

Based on the neuron in the terminus calcium movie, it appears that the voltage-gated Ca2+ channels are not evenly distributed, but be careful not to over-interpret a single experiment. Good science relies on reproducible data, and this movie is insufficient to establish firmly the distribution of voltage-gated Ca2+ channels. However, you can say that Ca2+ does not always fill the cytoplasm uniformly, because you have observed one exception. Regardless of their precise distribution, voltage-gated Ca2+ channels allow large numbers of Ca2+ ions to fill the small volume of cytoplasm with enough Ca2+ to initiate regulated exocytosis. In order to stop telling your muscles to contract, the neuron must be able to reduce rapidly the concentration of Ca2+ ions. As with the Na+ and K+ ion gradients, the Ca2+ ion gradient had been established by Ca2+ pumps located in the plasma membrane (see Jsmol of calcium pump). Therefore, all of the Ca2+ that flooded the cytoplasm from outside the cell must be returned rapidly back to the extracellular environment in order for your muscles to relax. Because pumps move ions more slowly than channels, there must be many pumps for every one voltage-gated Ca2+ channel.

Search the Internet to determine whether serotonin is produced only in Aplysia or in other animals as well.

Besides mammals, serotonin is found in all bilateral animals including worms and insects, as well as in fungi and in plants. Serotonin's presence in insect venoms and plant spines serves to cause pain, which is a side-effect of serotonin injection.

Why did they mix the serotonin with the dye? Why did the investigators have a constant flow of liquid across the cells? What could have gone wrong with this experiment if they omitted the dye and the flow of liquid?

By mixing serotonin with dye and providing a flow of liquid over the cells, the investigators could be certain that they had given serotonin to only one synapse. If they had not taken these precautions, it would be impossible to know if the serotonin had diffused from neuron A to neuron B.

You know how neurons reestablish the Na+ and K+ ion gradients after an action potential. Hypothesize what type of protein allows a neuron to reduce its cytoplasmic Ca2+ after the action potential has dissipated.

Ca2+ pump Embedded in the membrane of a neuron's secretory vesicles are proteins that can bind Ca2+. Their Ca2+ binding sites must be located in the cytoplasm and not inside the lumen of the vesicles because the increased Ca2+ ions are located in the cytoplasm (Figure 9.13C). A rise in Ca2+ leads to a new protein shape and the fusion of secretory vesicles to the plasma membrane. Upon fusion, a tunnel or opening forms between the membrane of the vesicle and the plasma membrane of the cell, and the opening grows in size until the vesicle becomes part of the plasma membrane and its contents are completely outside the cell (Figure 9.13B).

Explain why some polymers of glucose provide us with energy and others do not. Give a specific example of both types.

Cellulose does not provide energy to humans because we do not make an enzyme that can break the beta 1-4 covalent bond connecting adjacent glucose molecules in the polymer. We can break alpha 1-4 covalent bonds, releasing monomeric glucose molecules that we can harness for energy extraction.

What is the major source of increased muscle mass for plantaris muscles from both legs? Why did the right leg also increase in mass during these 2 months?

DNA is about 0.001 of the total dry mass. Therefore, most of the mass is protein, and the most abundant proteins in muscles are actin and myosin. The increase in actin and myosin indicates the muscles grew mostly by hypertrophy, though new cells did fuse to the existing cells (increases in DNA) which is hyperplasia in skeletal muscles. The investigators confirmed that the number of muscle cells did not change but the size of each cell was larger. What did increase is the number of nuclei in each muscle cell. The right legs increased in mass as well because the experimental rats were young, so plantaris muscles on both legs grew larger during the course of the experiment.

Explain the difference in outcomes between Figure 9.6 and 9.7 given that the equipment was unchanged between the two experiments. What role did threshold play in Figure 9.7?

Depolarization at one point in time did give the expected results because the action potential travels through the membrane and does not depolarize the entire membrane at on point in time but rather over an amount of time.once the membrane is locally depolarized to the threshold level or more, then the voltage-gated sodium channels open which causes the action potential to flow down the axon. In Figure 9.7, the depolarization wave moved down the length of the axon, and at each position, the membrane potential reached +45 mV. The magnitude of the action potential exceeded the initial stimulating voltage (application of +20 mV) because once threshold was reached in a local area, all of the neighboring voltage-gated sodium channels opened and the membrane potential was made less negative, causing more voltage-gated sodium channels to open. As with any form of diffusion, intracellular sodium ions spread to more voltage-gated sodium channels, and localized depolarization reaches threshold again but in a new area. This process produces a full action potential that will spread the entire length of the neuron. The propagation of an action potential is easy to see in an animation to the left.

Study the electron micrographs in Figure 9.13. Where on the secretory vesicle is the calcium-binding protein located that controls exocytosis? Use soap bubbles as an analogy for secretory vesicles to explain how exocytosis leads to the secretion of neurotransmitter. Be able to draw a picture of exocytosis.

Embedded in the membrane of a neuron's secretory vesicles are proteins that can bind Ca2+. Their Ca2+ binding sites must be located in the cytoplasm and not inside the lumen of the vesicles because the increased Ca2+ ions are located in the cytoplasm (Figure 9.13C). A rise in Ca2+ leads to a new protein shape and the fusion of secretory vesicles to the plasma membrane. Upon fusion, a tunnel or opening forms between the membrane of the vesicle and the plasma membrane of the cell, and the opening grows in size until the vesicle becomes part of the plasma membrane and its contents are completely outside the cell

Given how myosin polymers are organized and how myosin reaches over and binds to actin, what is the benefit of having actin spiral around? What is the functional consequence of each myosin rod surrounded by six actin polymers?

Figure 9.17 shows a thin, longitudinal slice of actin and myosin polymers. In cross section, myosin rod polymers are surrounded by actin on six sides, which ensures that myosin lobes will always have an actin binding site nearby. The myosin polymers project myosin arms in many directions so that each myosin can reach one of the six actin polymers surround it. the spiral nature of the actin polymer ensures that a myosin binding site will be facing in six directions and thus facilitate myosin binding from all six sides.

Is the use of PEDs cheating in sports? Explain your answer.

For many purists, PEDs violate the spirit of athletics, fail to recognize the natural talents of athletes, and lead to a pharmaceutical arms race by the athletes. If the authorities who make the rules consider the use of PEDs to be cheating, then athletes using PEDs are successful without putting in the hard work. Rules can change, but under today's rules, using PEDs to gain an advantage is cheating. Some people see athletes as role models, and role models who cheat are effectively endorsing cheating.

How is epinephrine involved in your fear response? Why would the release of glucose into your blood be an adaptive response?

From the overview, you have been told that epinephrine initiates the signal transduction in liver cells that results in the release of glucose into your blood, although you have not seen any supporting evidence yet. The release of glucose into your blood is adaptive, because if you need to run away or defend yourself, you will need the extra energy that glucose provides. Epinephrine is a hormone secreted by your adrenal gland anytime you have a fear or startle response (sometimes called fight or flight response). This hormone triggers a release of glucose from your liver so that all your cells have easy access to readily digested energy for running or defending yourself. Survival is necessary to reproduce, so having energy to survive is adaptive.

What enzyme is responsible for the production of glucose-1-phosphate from glycogen? Speculate why this enzyme is not called a kinase.

Glycogen phosphorylase uses free-floating phosphate in the cytoplasm and adds the phosphate to glucose when cleaving it from glycogen. The enzyme is not called glycogen kinase because the term kinase is reserved for enzymes that consume an ATP as the source of phosphate that is added to their substrates. Another enzyme will remove the phosphate from the glucose before it is secreted into your blood. Glycogen phosphorylase removes glucose monomers from glycogen and adds a phosphate onto the glucose as part of the removal process. This enzyme is not called a kinase because kinases phosphorylate proteins, not sugars.

Is glycogen synthase activated or repressed when it is covalently modulated by PKA? Support your answer with data in Figure 7.13.

Glycogen synthase was inactivated when it was covalently modulated by PKA, whereas phosphorylase kinase was activated by covalent modulation.

Explain in chemical terms why you can extract energy from starch but not cellulose although they are both composed of glucose polymers.

Human enzymes can bind to and break α 1-4 bonds but not β 1-4 bonds. Although wood and starch are both plant polymers composed of glucose, only microbes contain the enzymes necessary to digest β 1-4 covalent bonds. Because our genomes do not encode the same enzymes as other species, humans consider lettuce to be roughage, whereas other organisms can extract many calories from cellulose.

Compare and contrast hypertrophy and hyperplasia in muscle growth.

Hypertrophy refers to an increase in the size of individual muscle fibers, whereas hyperplasia refers to an increase in the number of muscle fibers. Research over the past 40 years has shown that the predominant mechanism for increasing muscle size is hypertrophy.

When a muscle cell is depolarized, what chemical signal is released in response? Speculate as to the adaptive value of T-tubules in muscle cells. What allows your muscles to relax once the neuron stops stimulating the muscle cell?

If muscle cells lacked T-tubules, the action potential could only reach SR membranes on the outer surface of the muscle cells, and the Ca2+ ions would slowly diffuse through the muscle, leading to a slow and uncoordinated muscle contraction. By winding throughout the cytoplasm, T-tubules ensure the depolarization reaches the entire cell evenly with the speed of an action potential. Relaxation is permitted by Ca2+ returning to the SR, troponin reverting back to its previous shape, and tropomyosin covering the myosin binding sites on actin.

Why did Kandel's group apply five separate puffs of serotonin to the sensory neuron's synapse with motor neuron A instead of just one puff? What evidence indicates that the synapse between the sensory neuron and motor neuron A had stored a memory?

If you look back at Figures 9.23 and 9.24, learning required multiple stimulations separated by short time intervals, which is why the scientists applied five puffs of serotonin instead of one long dose. The application of serotonin only to the synapse with neuron A (initiation) led to selective memory formation at the synapse between the sensory neuron and motor neuron A. Memory formation is indicated by the increase in physiological response by motor neuron A (Figure 9.27C, top panel, purple line), facilitation, but not by motor neuron B when their shared sensory neuron was electrically stimulated (Figure 9.27C, bottom panel, teal line).

What happened at the synapse between the sensory neuron and motor neuron B when it received one dose of serotonin after the synapse with neuron A had received five doses of serotonin (Figure 9.27C)? Use Figure 9.27 to define the terms initiation, facilitation, and capture that are defined in the paragraph below.

In a separate experiment, one dose of serotonin was delivered to the synapse between the sensory neuron and motor neuron B after five doses had been applied to the synapse with motor neuron A. The prior exposure of the sensory neuron's synapse A allowed the sensory neuron's synapse with motor neuron B to capture a long-term memory at synapse B (Figure 9.27C, bottom panel, purple line) that had been initiated at the sensory neuron's synapse with motor neuron A. The synapse with motor neuron B essentially captured a free ride from the sensory neuron's information processing at the synapse with motor neuron A. The enhanced action potential of neuron B after only one serotonin dose demonstrated the sensory neuron was able to store a second new memory at synapse B with less training. The five puffs of serotonin at synapse A had biochemically altered the sensory neuron's synapse to release more neurotransmitter onto neuron A (Figure 9.27C). initiation = application of neurotransmitter at a synapse that leads to either long-term or short-term memory formation facilitation = the deposition of new proteins at a synapse that received the initiation, the onset of long-term memory formation capture = long-term memory formation via deposition of new proteins at a second synapse that benefited from facilitation at another synapse

What role does calcium play in a neuron's function?

In neurons, calcium is the ultimate multitasker. It helps propagate electrical signals down axons. It triggers synaptic terminals to dump their cargo of neurotransmitters into synapses. And, if that's not enough, it's also involved in memory formation, metabolism, and cell growth.

Use Figure 7.5 to list the steps of the fear response and what type of modulation triggers each step.

In this process your cells need to move chemical information from outside the cells to inside the cells.This process is called signal transduction. Starts with epinephrine which contains 2 of the 4 common electronegative elements N, O, P, S and it is hydrophilic, meaning it cannot cross any membranes containing phospholipid bilayers.Epinephrine binds to the epinephrine receptor which causes a change in shape of the receptor.When the receptor changes shape it can interact with the G protein.Activation of the G protein transmits the information into the cytoplasm.Activated epinephrine makes the G protein dissociate into two parts.The yellow subunit releases an old GDP, binds to a new GTP, and dissociates into from the other two subunits of the G protein.GTP allows fee floating of the G protein subunit to interact with a different protein called adenylyl cyclase.Adenylyl cyclase converts ATP into cyclic AMP or cAMPcAMP is a small molecule that diffuses throughout the cytoplasm until it binds and activates another protein, protein Kinase A (PKA)PKA has two functions in the pathway1st-- PKA activates phosphorylase kinase, PKA consumes ATP to activate phosphorylase kinase by phosphorylation.Phosphorylase kinase consumes an ATP to activate glycogen phosphorylase. Finally, glycogen phosphorylase removes one glucose from glycogen and adds a phosphate on carbon #1 of glucose to produce glucose-1-phosphate.2nd-- glycogen synthase is phosphorylated by PKA

Examine Figure 9.22, and describe the trends in plantaris muscle DNA and dry mass where gastrocnemius muscle has been removed (left leg) in comparison to legs where the two muscles were both left intact (right leg). Approximately what proportion of the total dry mass was DNA (note the different units on the y-axes)?

It is important to note that the experimental rats were young, so plantaris muscles on both legs grew larger during the course of the experiment. Muscle growth on the control right side illustrates the importance of the sham operation as an experimental control. As you can see from the data, the plantaris muscles on the left side were heavier than the same muscles from the sham-operated right side. Although we do not have statistical analysis with p values, you can tell that the total muscle mass from left plantaris muscle appears to be significantly larger (considering the standard deviation) than the control muscle 60 days after the surgery. The mass of the plantaris muscle DNA also increased, but if you look at the scales for the two graphs, you can see the DNA is about 0.001 of the total dry mass. Therefore, most of the mass is protein, and the most abundant proteins in muscles are actin and myosin.

Some enzymes are regulated in complex ways, as you can see in Figure 7.14A. Summarize the effect on phosphorylase kinase activity when its α and β subunits are covalently modulated by multiple phosphates. How many phosphates can be added to the α and β subunits? Support your answer with data.

It is impossible to predict the consequences of phosphorylation, so each modified enzyme must be tested individually. Phosphorylase kinase was modulated in two ways. The first and rapid activation happened when the β subunit acquired one phosphate (red line). The slower activation that continues to increase phosphorylase kinase's capacity happened when the α subunit acquired first one and then a second phosphate (blue line). The γ subunit is allosterically modulated by the covalently modulated β (red line) and α (blue line) subunits. This two step, indirect modulation of the γ subunit (green line) of phosphorylase kinase by its two regulatory β and α subunits permit a flexible response to low and high levels of epinephrine depending on the degree of perceived fear.

How did Kandel demonstrate that Aplysia sea slugs were able to learn?

Kandel and his team soon identified a simple defensive reflex in the slug similar to the human reflex to quickly pull one's hand away from a hot object. Scientists once thought that only higher order animals could learn, but Kandel soon showed that slugs could be taught to modify this reflex. Kandel and his collaborators repeated many of these Aplysia experiments with mice, and found that mammals and sea slugs share the same genes (orthologs) responsible for short- and long-term memory formation and storage (Figure 9.28).

Explain how the use of PEDs by some athletes creates an arms race among athletes.

Legalization would permit uniform education for athletes and regulation of which PEDs can be used, and how much. A better use of testing program money might be to develop safer PEDs that would be sanctioned by sports authorities. If PEDs were allowed within a particular sport, universal access would level the playing field. Ironically, the stated reason for taking PEDs in the first place is to gain an advantage, and this would no longer be true if every athlete had equal access to the PED. Sanctioned PEDs would satisfy the IOC's equality principle, but not every athlete would have equal access to the drug due to costs, availability, or health concerns. Furthermore, because steroids regulate gene activity, it is not clear that it ever would be safe to inject steroids above normal levels.

What new physical structures are produced on the neuron's plasma membrane that allow long-term memories to persist much longer than short-term memories? Relate these structures to long-term memory's requirement for new protein production.

Long-term memory formation includes additional capacity for exocytosis of neurotransmitter as depicted by gray triangles binding to membranes at synapses near the bottom of Figure 9.26. Long-term memory is the emergent property produced when cells sustain their increased capacity for exocytosis in response to persistent training. Once the level of activated PKA is reduced, CREB-2 becomes dephosphorylated and resumes its inhibition of CREB-1 which is also dephosphorylated, and the production of new proteins for long-term memory is stopped. Any exocytosis-related proteins produced before inhibition of CREB-1 will be deposited on the plasma membrane, and long-term memory will have been established. Production of phosphorylated CREB-1 homodimer is the tipping point for conversion from short- to long-term memory.

Define facilitation and capture as used in Figure 9.27. Describe at least two physical changes that happen at nerve synapses that you would see after memory formation.

Memories are stored initially in the hippocampus, where synapses among excitatory neurons begin to form new circuits within seconds of the events to be remembered. An increase in the strength of a relatively small number of synapses can bind connected neurons into a circuit that stores a new memory. facilitation = the deposition of new proteins at a synapse that received the initiation, the onset of long-term memory formation capture = long-term memory formation via deposition of new proteins at a second synapse that benefited from facilitation at another synapse

When sea slugs were given drugs that blocked protein translation, they could not form long-term memories but they could form short-term memories. What do these results tell you about short- and long-term memory formation?

Memory comes in two forms—short term and long term. Short-term memory is the consequence of minimal stimulatory input, whereas long-term memory is the consequence of repeated input. Short-term memory (for example cramming for a test) only lasts for minutes to a few hours, whereas long-term memory lasts from days to years. Short-term memory does not require any new protein production but long-term memory does. These distinctions between short- and long-term memory were key insights that opened the way for Kandel and his collaborators to understand how neurons produce memories.

Speculate what genotypes might be present in a person who cannot form long-term memories. What genotypes might produce someone with photographic memory?

Memory involves many genes, but based on Figure 9.26, you could predict that people with dominant phosphatase alleles would be less likely to form long-term memories. Similarly, people who cannot form long-term memories might have problems producing CREB-1 homodimers, and/or the protease but not the exocytosis proteins, because they can secrete neurotransmitters for short-term memories. Conversely, you would expect people with photographic memories to possess dominant alleles of PKA, MAPK, CREB-1 or the protease, and perhaps two recessive alleles of CREB-2, the phosphatases, or the enzyme that destroys cAMP, which you learned about in Section 7.2. Many other genes are involved as well, but these genes are likely candidates for the two extremes of long term memory formation, and it would be interesting to study the alleles in people with different capacities for long term memory formation.

Why do the white sarcomere bands get smaller while the dark band stays the same size? Use Figures 9.16 through 9.19, and online movies linked from this chapter, to help you construct a mental picture of how sarcomeres contract.

Muscle contraction occurs as millions of sarcomeres contract. As myosin pulls on actin, the light band of actin is drawn toward the dark band of myosin. The light bands on both sides disappear because actin polymer rods are sliding between the myosin polymer rods, which do not move. The myosin rods do not move because there are equal numbers of myosin molecules on both ends pulling in opposite directions. The thinner, rope-like actin polymer rods are pulled by myosin toward the center of the sarcomere from either side.

What is myelin? What impact does it have on the function of nerve cells?

Myelin is an insulating layer, or sheath that forms around nerves, including those in the brain and spinal cord. It is made up of protein and fatty substances. This myelin sheath allows electrical impulses to transmit quickly and efficiently along the nerve cells. If myelin is damaged, these impulses slow down.

Approximate how many more Na+/K+ pumps than voltage-gated sodium channels you would expect to find in the plasma membrane of a neuron. Base your answer on their different rates for transporting ions.

Neurons need up to 10,000 times more Na+/K+ pumps as voltage-gated sodium channels to match ion transport rates. This simple calculation tells you that different membrane proteins must be produced in different amounts, and their densities in the plasma membrane vary over several orders of magnitude (powers of 10, 10N). The much more abundant but slower Na+/K+ pumps help reset the resting membrane potential over a longer time period than the potassium ion channels do. Although a neuron can send another action potential before the ion concentrations described in Table 9.1 are fully reestablished, the details of this rapid ability for a second action potential are beyond the scope of this book. These four types of proteins (a ligand-gated Na+ channel, two types of voltage-gated ion channels, and a Na+/K+ pump) play important roles in the electrical communication in neurons.

Summarize the two different types of communication systems used by neurons and where each of these takes place in a neuron. Which of these communication systems ultimately triggers muscle contraction?

Neurons use electrical communication to move information down their lengths as rapidly as possible. Chemical communication informs a neuron what action it should take and what action it should pass on, such as telling a muscle cell to contract

Can energy be created or destroyed? Explain your answer in terms of eating food for energy. What law of physics addresses this concept?

No, the first law of thermodynamics states energy is not created or destroyed when you eat, it is simply converted from one form to another. Some will be captured in new chemical bonds but some will be last as waste heat or randomness.

How many cAMP molecules does each PKA need to become activated? Base your answer on data in Figure 7.11.

Once PKA has been allosterically activated by two (approximate slope in Figure 7.11C) cAMP molecules

Does PKA preferentially phosphorylate either glycogen synthase or phosphorylase kinase? Support your answer with data in Figure 7.12. Speculate how PKA "knows" which amino acid to phosphorylate.

Once PKA has been allosterically activated by two (approximate slope in Figure 7.11C) cAMP molecules, PKA phosphorylates both substrates with equal efficiency, and random diffusion in the cytoplasm is the only factor that determines which substrate it will phosphorylate next. The particular serine that is phosphorylated on both substrates is determined by the shape of the active binding site in PKA and by which amino acids on the substrates are positioned to receive the terminal phosphate from ATP. Neither the substrate nor the kinase "know" which amino acid should be phosphorylated. The shape of the proteins determine which amino acid is in the right spot and has the right shape for PKA to generate a new covalent bond on the correct serine for a given substrate.

Make a list of the four hallmarks of molecular signal transduction in cells. Use Figure 7.5 to cite a specific example of each, and use the data in Figures 7.6 to 7.14 for support.

Prokaryotes, plants, and animals all share the same four hallmarks, although the molecular details will vary. The four hallmarks are amplification, specificity of shape, modulation of protein shape and function, and the ability to turn off every step in the pathway.

How does allosteric modulation change the function of a protein?

Proteins that are allosterically modulated often interact through weak ionic bonds or weaker H-bonds. Some allosteric modulators are hydrophobic, and they bind to their target proteins via hydrophobic side chains. Hydrophobic interactions can be disrupted by detergents or hydrophobic solvents, such as oils. Covalent modulation, however, is much more durable and is typically removed only when an enzyme, such as a phosphatase, breaks the bond holding the phosphate in place.

Look at the amino acids in Figure 7.2. Which three amino acids are possible targets for covalent modulation because they terminate in an OH group? Explain in chemical terms why phosphorylation of a protein can change its shape.

Proteins typically contain all twenty amino acids, but only three can be covalently modified by kinases. Because phosphates require terminal OH groups, only serine, threonine, and tyrosine are suitable substrates for kinases. Looking at their structures, you may have suspected that some kinases specialize in phosphorylating either serine or structurally similar threonine, whereas a different class of kinases phosphorylates the much larger tyrosine side chain. Kinases have active sites that fit particular amino acid substrates. As is often the case at the molecular level, a particular size of an active site does not fit all amino acids.

Based on your previous exposure to chemistry, define oxidation and reduction. For this definition, restrict your answer to the movement of electrons.

Reduction is the accumulation of electrons (e-)which you can remember because the reduced atom becomes more negatively charged by the electron. Oxidized molecules give up the electrons. When one molecule becomes oxidized, something else must become reduced.

Describe the role of the protease produced during long-term memory formation. Describe any positive feedback loops or negative feedback loops present in long-term memory formation.

Remember, long-term memory requires new protein production. The protease is translated in the cytoplasm, and it cleaves the oval regulatory subunit of PKA, liberating more activated PKA. Therefore, activated PKA is part of a positive feedback loop that enhances its own activation as long as sufficient serotonin stays bound to its receptor. The

Serotonin receptors are embedded in the plasma membrane and interact with G-proteins. Speculate what additional molecules might be involved in memory formation (see Figure 7.5 to recall signal transduction with G proteins).

Serotonin produced in response to mild electrical shocks to the tail were secreted onto the sensory neuron and bound to its receptor. The receptor changes shape and activates several copies of a G-protein (G), which activates several copies of adenylyl cyclase (AC). Within a second, many cyclic adenosine monophosphate (cAMP) second messenger molecules accumulate at the site of the serotonin receptor. cAMP activates PKA by dislodging the purple oval regulatory subunits from the rod-shaped catalytic subunits. Once the catalytic PKA subunits are released from their regulatory subunits, local calcium ion channels are phosphorylated as are proteins in the membranes of vesicles responsible for permitting exocytosis of neurotransmitters.

Define signal transduction, and explain why it is necessary in the fear response.

Signal transduction conveys hydrophilic molecular information from the extracellular environment to the intracellular. It is necessary to move the information across a plasma membrane. Signal amplification is whenever transduction happens amplification the emphasizes the reaction

Read about muscle anatomy to realize how muscle cells are bundled together to form muscles, such as your bicep. What cellular features make skeletal muscles unusual compared to most cells?

Skeletal muscle cells are very unusual because of their gigantic size and their extensive production of proteins used to contract muscles. Skeletal muscles are also unusual because they are multinucleated, meaning each cell can contain hundreds of nuclei. {Connections: You learned about giant bacterial cells that amplify their DNA in Section 8.1.} Muscle cells are the product of many smaller precursor cells fusing together. The number of nuclei in a muscle cells tells you how many precursor cells fused to form the much bigger muscle cells. The number of nuclei varies depending on how big the muscle cells are. Longer muscles will contain longer cells and therefore more nuclei. A muscle can be thought of as the summation of many long, skinny muscle cells bundled together to function as a cohesive tissue. Within each cell are the repeating sarcomere units. Each multinucleated muscle cell contains hundreds to millions of sarcomeres, depending on the size of the muscle cell. You will read more about sarcomeres later. Four characteristics define skeletal muscle tissue cells: they are voluntary, striated, not branched, and multinucleated. Skeletal muscle tissue is the only muscle tissue under the direct conscious control of the cerebral cortex of the brain, giving it the designation of being voluntary muscle.

Look at the Na+/K+ pump cycle in Figure 9.3B. Describe the type of modulation, covalent or allosteric, in each step and the functional consequence of each shape change caused by the modulation.

The Na+/K+ pump changes its shape in response to covalent modulation when it is phosphorylated or dephosphorylated. Figure 9.3B illustrates the steps. The pump (1) is allosterically modulated when it binds three sodium ions (2), which leads to ATP binding and phosphorylation (3). Once phosphorylated, the covalently modulated pump has a shape change in the transmembrane domains and develops a low affinity for Na+. The pump opens toward the extracellular world and lets go of the three sodium ions toward the outside of the cell (4), which causes another shape change. Now the pump has a high affinity for two potassium ions (5), which bind from the extracellular environment to allosterically modulate the pump again. Upon binding two potassium ions, the pump breaks its covalent bond to the phosphate (6), which reverses the covalent modulation from step 3. The transmembrane domains move again, close the opening on the extracellular side, produce an opening on the cytoplasmic side, and the pump develops a low affinity for K+. The pump releases the two K+ ions into the cytoplasm, which allosterically modulates the pump again, and the cycle repeats (1).

Why do myelinated axons transmit electricity faster? Explain why nodes of Ranvier would not work if they were spaced too far apart.

The benefit of myelin is only realized if nodes of Ranvier are appropriately spaced. The spacing of the nodes allows waves of sodium to flood the axon cytoplasm and spread to the next node where more voltage-gated sodium channels are available to open. Myelin covers most of the membrane, so ions cannot enter the cytoplasm except at the nodes. In axons without myelin, all of the ion channels can open, and this would take longer for the action potential to move gradually down the axon because incremental movement down the axon would be much shorter than the bigger steps between Nodes.

Look up the drug digitalis on the Internet, which was originally purified from a flower called foxglove. To what protein does this heart medication bind, and what happens to this protein once digitalis binds (see mechanism of action)?

The heart medication, digitalis, works by stalling a dose-dependent subset of your Na+/K+ pumps so that they cannot transport ions any more. The net result is a reduction of membrane potential closer to -50 mV with more sodium inside the cells than normal.

Did the plantaris muscles grow by hypertrophy (enlarged size) or hyperplasia (more nuclei)? Support your answer with data from Figure 9.22.

The increase in actin and myosin indicates the muscles grew mostly by hypertrophy, though new cells did fuse to the existing cells (increases in DNA) which is hyperplasia in skeletal muscles. The investigators confirmed that the number of muscle cells did not change but the size of each cell was larger. What did increase is the number of nuclei in each muscle cell.

Do the pencil-like muscle proteins look randomly distributed or organized in a regular pattern? Explain your answer.

The positioning of the dark and light protein rods in the cross section is not random. You can see that the thicker protein rods are distributed in hexagonal patterns with one dark rod in the middle. Furthermore, six lighter protein rods surround each darker protein rod to produce a maximally packed interleafing of two proteins that are essential to muscle contraction.

What processes allow a neuron to be stimulated a second time? What prevents action potentials from "echoing" back up the axon?

The refractory period prevents an echo of the action potential. This resting time allows the area of depolarization time to depolarize and become responsive again.

Do molecules become more or less disordered on their own? What must be supplied to a system that is producing molecules of increased order? What law of physics addresses this concept?

The second law of thermodynamics states molecules become more disordered over time unless energy is applied to maintain order.

What are some of the basic structures and functions of skeletal muscles? Watch this muscle movie to see four rows of sarcomeres contract inside of a single muscle cell.

The skeletal muscles are organs Each cell in the skeletal muscle tissue is a single muscle fiber. The cell membrane of the skeletal muscle cell is known as sarcolemma while the cytoplasm of the skeletal muscle cell is also known as sacroplasm produce skeletal movement, maintain posture and body position, support soft tissues, guard entrances and exits, maintain body temperature, store nutrients muscle cells = muscle cells are different in that they do not divide like most cells in your body.

Describe how different channels opened for different durations as in Figure 9.10. Use Figure 9.8A to address why the number of open channels diminishes even though the stimulating signal is still on.

The summation response at the bottom of Figure 9.10 terminates even though the box-like stimulus persists longer. The reason the current ends is that gradually, the 100 ion channels used for this figure go into the refractory period and cannot open again until later. By the time the refractory period is over, the original stimulus had been terminated by the investigator and we only saw a single summation wave of open channels.

Diagram the chemical reaction for adenylyl cyclase.

epinephrine--epinephrine receptor---GDP to GTP---G protein---adenylyl cyclase

The epinephrine receptor was first called the β-adrenergic receptor. Look up "beta blockers" on the Internet to see their clinical uses. Metoprolol was antagonist #2 in Figure 7.6. Why do you think this class of medicine is called a beta blocker?

Through allosteric interactions, epinephrine initiates a series of movements in its receptor's amino acids to cause a new shape in the epinephrine receptor. Epinephrine antagonists are called beta blockers because they bind to β-adrenergic receptors. Antagonists bind to the receptor but do not allow the receptor to change its shape and become activated. The receptor is not activated when metoprolol binds, which is used clinically to regulate heart rhythm and high blood pressure. In response to epinephrine binding, the receptor's cytoplasmic domain exhibits a new shape and thus a new function. With this signal transduction, epinephrine's hydrophilic message has crossed the membrane without the ligand having to traverse the membrane directly.

Compare the duration of the input stimulus and the neuron's response in the right half of Figure 9.5B. Speculate how the duration of the neuronal depolarizations can be greater than the duration of the activating electrical impulse.

Through experiments similar to Figure 9.5, physiologists had discovered that neurons require a threshold level of stimulation before they will propagate their own electrical impulse down their axons. When a neuron is stimulated at least as high as the threshold, then the cell produces a complete wave of depolarization. The duration of a wave of depolarization is longer than the stimulating impulse because many more ion channels open over time and allow more sodium ions to diffuse to the next zone of voltage-gated sodium channels, which also open in response to threshold depolarization. The longer action potential is similar to the longer time that it takes for a stadium wave to move past any given point than it took for one person to stand up and sit down.

Speculate how action potentials are prevented from traveling back up the axon once they reach the nerve terminus.

To prevent an echo of the action potential from bouncing back to the site of its origin, all voltage-gated sodium channels have a refractory period of time when they cannot open even if the local threshold depolarization is exceeded. The area of depolarization has time to repolarize until the channels have "rested" long enough to become responsive again to local depolarization. Unlike a stadium wave, neuronal action potentials are one-way phenomena, and they do not move backward to the area of the original stimulation.

How does tropomyosin prevent your muscle cells from contracting all the time? How does troponin regulate muscle contraction? What happens to troponin and tropomyosin when muscle cells relax?

Tropomyosin blocks myosin binding sites on actin molecules, preventing cross-bridge formation and preventing contraction in a muscle without nervous input. Troponin binds to tropomyosin and helps to position it on the actin molecule; it also binds calcium ions.

What is a voltage-gated ion channel? How does channel differ from an ion pump? List all of the voltage-gated ion channels you studied in this section.

Voltage gated ion channels are channels that open when there is a change of the voltage in the neuron opposed to opening when there are ions present, as the ion pump does. The voltage gated ion channels we have learned about are the Sodium and potassium.

It is essential that you understand the data in Figure 9.23B. Did the gill retract more because the electrical shock caused the muscle to contract more? What role did the electrical shock play in memory? Does learning require the input of electrical shocks? Hypothesize what caused Aplysia to retain the memory longer and to increase the duration of gill retraction.

When Kandel touched the siphon with a pointed object, Aplysia withdrew its siphon and its gill to protect them from harm. If Kandel touched the siphon slightly before he applied a mild electrical shock to the tail, the animal retracted the siphon and gill to a greater extent (Figure 9.23B). A stronger retraction in Aplysia is similar to your friend hearing a loud noise and then jumping later when you touch his shoulder. After this shock/touch training, when Kandel lightly touched the siphon in the absence of a shock, the animal responded as if it has been shocked. In other words, the sea slug learned to associate the shock with the touch. The purpose of the electrical shocks was not to cause muscles attached to the gill and siphon to contract. The shock provided a noxious stimulus that the slug could learn to associate with lightly touching its siphon. The investigators could have pinched the animal's tail, but electrical shocks were easier to reproduce and deliver. Learning does not require electrical shocks; any noxious stimulus could have been used. Electrical shocks were convenient and permitted careful regulation over their intensity so that the animal would not be harmed. Once the animal was trained, no electrical shock was used to produce the data in Figure 9.23B. The gill was retracted further and for a longer time after more training sessions because the animal established a long-term memory that associated an unpleasant sensation with the gentle touch to its siphon.

What happens to a neuron that is stimulated below threshold depolarization? What happens when a neuron is stimulated above threshold? In Figure 9.5, what is the approximate threshold for this particular human neuron?

When a cell was depolarized by only 10 mV (red inset), the measuring electrode (purple graph) detected exactly what was applied to the cell, and the voltage decayed over time.However, when the neuron was depolarized by 20 mV, something very different happened. The output current was much greater than the input current, and the membrane potential increased by 120 mV to a maximum of +50 mV! In Figure 9.5, threshold appears to be approximately -50 mV, or a change of + 20 mV. At threshold depolarization, the voltage-gated sodium channels open, and they contribute further to the local depolarization until the membrane potential is inverted to about +45 mV. Positive 45 mV represents the full depolarization for the cell in Figure 9.5.

What molecular interactions and shape changes activate a G protein α subunit? What causes the α subunit to become inactive? Support your answers using Figure 7.9.

When the epinephrine receptor is allosterically modified by epinephrine, the receptor changes its shape which allosterically changes the shape of the G protein α subunit. The alpha subunit releases its bound GDP and binds to a new GTP which activates the alpha subunit and causes it to move away from the β/γ subunits. The α subunit becomes inactive when it cleaves the terminal phosphate away from GTP which becomes GDP and the phosphate floats away. When the α subunit is bound to GDP, it reassociates with the β/γ subunits.

Describe how the gated ion channel in Figure 9.4 works using an analogy of an automated revolving door representing the ion channel and people entering a building through the door representing the ion gradient. What causes the gate/door to open and close?

When the ligand binds, the ion channel allows only sodium ions to flow down their chemical and electrical concentration gradients into the cytoplasm. Ion channels are not as specific as enzymes, but they are selective. Only ions of a particular charge and atomic radius can fit through the pore of any given ion channel.

Where is sodium more abundant, inside or outside of a cell? Where is potassium more abundant? For each ATP consumed, how many ions does the Na+/K+ pump move across the plasma membrane? What is the change in electrical charge for a cell when the pump completes one cycle of pumping?

When your neurons and muscles are resting, they have thirty times more potassium in their cytoplasm than on the outside, and twelve times more sodium outside compared to inside. Na+/K+ pumps help maintain these ion gradients as a form of potential energy that can be used later. {Connections: Ion gradients across a membrane as an energy source was in Chapter 4.4 about abiotic energy harvesting.} For every ATP consumed, the Na+/K+ pump moves three sodium ions out of the cell and two potassium ions into the cell. This 3:2 ratio is a vital ion ratio, because it contributes to the electrical potential every animal cell on the planet needs to perform a wide range of functions. By exporting one more Na+ than the number of K+ ions exported with each Na+/K+ pump cycle, the cytoplasm gradually becomes more negative compared to the extracellular world. One ion at a time, cells accumulate an overall membrane potential, which is a separation of charged particles in the form of ions such as Na+ and K+. Animal cells have a resting membrane potential that can range from -20 to -200 millivolts (mV), although the precise number varies by cell type and species. You can see an online animation summarizing membrane potential, including the "leak" of K+ out of the cytoplasm.

Based on its structure in Figure 7.4, do you think epinephrine is hydrophobic or hydrophilic? What must happen to carry the information of fear in epinephrine across the plasma membrane of your liver cells?

You can tell that epinephrine is hydrophilic because it contains three oxygen atoms and one nitrogen atom, which are electronegative and thus participate in polar covalent bonds. To communicate its information across liver cell membranes, epinephrine must bind to a protein receptor that changes its shape due to allosteric modulation by the ligand epinephrine With its three oxygens and one nitrogen, epinephrine appears to be hydrophilic and thus not able to diffuse through a plasma membrane. For the information of epinephrine to enter your liver cells, it will need the help of a protein that spans the plasma membrane - the epinephrine receptor.

Interpret the data in Figure 9.22 to explain how muscle cells respond over the long term to consistent exercise.

You should recall that muscle cells are different in that they do not divide like most cells in your body. The increased DNA shows that new precursor cells fused with the existing muscle cells, which is a sign hyperplasia in skeletal muscles. The muscles increased their protein (hypertrophy) and DNA (hyperplasia), so getting bigger muscles in response to exercise involves two processes simultaneously.

If muscles have the same signal transduction pathway, why do you need a duplicate pathway in your liver? Hypothesize whether every cell in your body is able to respond to epinephrine by releasing glucose. What experiment could you perform to determine which cells do respond?

Your liver stores more glycogen than your muscle, but your liver does not directly influence movement of your body. Your muscles quickly exhaust their supply of glycogen, and the liver provides more glucose to function like an extra tank of gasoline for a car. Every cell in your body is bathed in epinephrine from your blood, but most cells do not respond to the fear signal. Only those cells that produce epinephrine receptors on their plasma membranes are able to bind to the fear hormone. If you wanted to determine which cells in your body responded to fear, you could take small biopsies of each tissue and see which cells bound to an antibody that has a high affinity for the epinephrine receptor. {Connections: You learned about antibody affinity in Section 5.3.} If you tagged the antibodies with a fluorescent dye, you could visualize cells with the receptor. The process of using antibodies to detect proteins on cells is called immunofluorescence. Immuno- refers to the use of antibodies, and fluorescence refers to the glow in the dark dye coupled to the antibodies.

What is the final product of the fear response that serves as a survival mechanism?

glucose-1-phosphate

Categorize the different amino acid side chains based on their chemical structures: hydrophilic, hydrophobic, acids, or bases.

hydrophobic: side chains that contain only carbon and hydrogen hydrophilic: contain either nitrogen, oxygen, or sulfur at the extreme ends of their side chains and are hydrophilic acids: have O, CH2, and H2C groups (can participate in ionic bonds) bases: have CH2, NH3, H2N groups (can participate in ionic bonds)

Use Figure 9.26 to explain the role each type of molecule plays in long- and short-term memory: serotonin receptor, G proteins, cAMP, PKA, MAPK, protease, CREB-1, CREB-2, and the secretory pathway proteins.

serotonin receptor = "The study found that serotonin enhances the speed of learning," explains study co-author Zachary Mainen, from the CCU. "When serotonin neurons were activated artificially, using light, it made mice quicker to adapt their behavior in a situation that required such flexibility," he adds G proteins = cAMP = cAMP regulates memory formation mainly by activating the cAMP-sensitive PKA. PKA = cAMP regulates memory formation mainly by activating the cAMP-sensitive PKA. Once activated, PKA can then phosphorylate various downstream kinases and transcription factors required for memory formation (Abel and Nguyen 2008). MAPK = MAPK pathways relay, amplify and integrate signals from a diverse range of stimuli and elicit an appropriate physiological response including cellular proliferation, differentiation, development, inflammatory responses and apoptosis in mammalian cells. protease = The protease is translated in the cytoplasm, and it cleaves the oval regulatory subunit of PKA, liberating more activated PKA. Therefore, activated PKA is part of a positive feedback loop that enhances its own activation as long as sufficient serotonin stays bound to its receptor. CREB-1: . CREB-1 is a transcription factors that activates many genes; only two genes are shown for simplicity. CREB-2: CREB proteins in neurons are involved in the formation of long-term memories and long-term potentiation. CREB2 is also known as Activating Transcription Factor 2 (ATF2). CREB2 is a CREB repressor, which means it inhibits long-term memory formation. The four steps to long-term memory formation are: 1. Serotonin modulates proteins near the input to release more neurotransmitter when the neuron is stimulated (initiation). 2. Signal transduction leads to the activation of PKA and short-term memory formation. 3. If PKA activation is prolonged due to repeated stimulation, MAPK moves to the nucleus of the cell and stimulates a cascade of genes and leads to new protein formation (facilitation). 4. PKA also marks all synapses in the sensory neuron for possible capture via new protein deposition, which can lead to new physical structures and swellings at a distant synapse despite lower serotonin exposure.

Compare and contrast calcium, sodium, and potassium ion channels used in neurons.

sodium: calcium: potassium: