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ch 10,11,12,13,14

Terms in this set (140)

Which of the following is NOT a biological advantage of enzyme cascades?
the ability to process widely different incoming signals
How are the allosteric properties of ATCase and hemoglobin similar?
The quaternary structure of both proteins is altered by binding small molecules
Enzymes that are activated by specific proteolytic cleavage are called
Zymogens
The activity at a single functional site of an allosteric enzyme _____ the activity at others.
affects
Enzymes that catalyze the same reaction but differ in amino acid sequence are called
isozymes
What is the function of protein phosphatase?
turning off the signaling pathways
Allosteric enzymes are different from non‑allosteric enzymes because allosteric enzymes
exhibit a threshold effect where the response to substrate concentration changes significantly
Protein kinases generally regulate the activity of target proteins by transferring a phosphate group from ATP to the target protein. To what amino acid functional groups are these phosphates transferred?
hydroxyl groups
The binding of the substrate to the active site activates all other active sites according to the
concerted model
When an allosteric enzyme is directly affected by a molecule that is not its substrate, this effect on the enzyme is called
heterotropic effect
The inhibition of aspartate transcarbamoylase by cytidine triphosphate (CTP) is an example of
feedback inhibition
Feedback inhibition is important for the regulation of many metabolic pathways. Which of the statements are examples of feedback inhibition?
The beginning of glycolysis is inhibited by high levels of ATP in the cell and the production of tryptophan is halted by the presence of excess tryptophan
Which of the following statements describes a dimeric allosteric enzyme following the concerted model?
The equilibrium between the T state and R state favors the T state
The RR form of the enzyme is the most active
The enzyme can exist as an RR dimer
A histidine residue in the active site of aspartate transcarbamoylase, or ATCase, is thought to be important in stabilizing the transition state of the bound substrates. Predict the pH dependence of the catalytic rate, assuming that this interaction is essential and dominates the pH activity profile of the enzyme.
The Henderson-Hasselbalch equation is pH=p𝐾a+log[A−][HA]pH=pKa+log[A−][HA]
The p𝐾apKa of an unperturbed histidine side chain in a protein is about 6.5.
At what pH is the reaction rate expected to be half maximal?
6.5 and the ATCase activity will decrease as the pH increases
What are characteristics of allosteric enzymes?
They undergo conformational changes as a result of modulator binding
They may have binding sites for regulatory molecules that are separate from active sites.
They generally have more than one subunit
An allosteric enzyme that follows the concerted mechanism (MWC model) has a T/R ratio of 300 in the absence of substrate. Suppose that a mutation reversed the ratio.
Note that R is the highly active form of the enzyme and T is the less active form of the enzyme.
Select all of the effects this mutation will have on the relationship between the rate of the reaction (V) and substrate concentration ([S])
The plot of V versus [S] would be shaped like a hyperbola.
The enzyme would be more active.
The enzyme would likely follow Michaelis-Menten kinetics.
Which statements about isozymes are true?
Isozymes have different amino acid sequences
Isozymes are present in various developmental stages
Lactate dehydrogenase is an example.
The proteolytic enzyme trypsin is produced in the pancreas as the zymogen trypsinogen. Trypsinogen is cleaved to yield the active form. Trypsin, in turn, activates other pancreatic zymogens.
Select every enzyme that is used in the activation of trypsinogen
trypsin
enteropeptidase (enterokinase)
Select every pancreatic zymogen that is directly activated by trypsin
procarboxypeptidase
proelastase
prolipase
chymotrypsinogen
What is the mechanism by which adenylate cyclase stimulation by Gα is terminated?
hydrolysis of GTP by the Gα subunit
Why are membrane receptor proteins often used to transfer information from the cell's external environment to its interior?
The signal molecule is too large and/or too polar to pass through the cell membrane
How does calcium binding allow calmodulin to interact with its target proteins?
Calcium ion binding changes the conformation of calmodulin, exposing alpha helices that can bind to target proteins
Small molecules and proteins can act as cellular communication signals by binding to cell receptors.
A protein binds to its receptor on a cell surface and starts a biochemical chain reaction within the cell.
What is the general term for this type of pathway?
signal transduction
What is a receptor protein?
a plasma membrane protein that binds with chemical signals
What happens in the reception phase of cell signaling when protein signal molecules are present?
Specialized cell surface proteins bind to specific protein signal molecules outside the cell
The regulation of many intracellular biochemical processes is mediated by calcium due to
the binding of calcium to calmodulin
What happens in the transduction phase of cell signaling when protein signal molecules are present?
Signal molecules induce a change in membrane proteins that activates other proteins within the cell
What is the role of second messengers in signal‑transduction pathways?
small molecules or ions that relay a signal from the cell's surface to the cell's interior
Which of the following events contributes to the termination of a signal generated by the binding of a ligand to a receptor tyrosine kinase?
Phosphatases hydrolyze key phosphorylated residues
Which of the following steps would occur immediately after epinephrine binds to the β-adrenergic receptor?
GTP displaces GDP in Gαs
Signal transduction is part of a cell's response to an external signal. Although signal transduction pathways can differ in their details, there are some common elements.
A receptor may pass on a signal by interacting with another protein or by acting as an enzyme.
Signal transduction cascades, often involving protein kinases, amplify a signal intracellularly.
A second messenger may carry a signal from the cell membrane to an organelle.
Signal transduction cascades directly transmit a single stimulus to a single target.
A ligand, such as a hormone, binds to a specific cell surface receptor on a target cell.
A receptor changes conformation upon binding, transmitting a signal across the cell membrane.
Phosphatases remove phosphoryl groups from polypeptides, regulating a cell's response.
Releasing of glucagon into the blood to the promotion of glycogenolysis.
1. Glucagon binds extracellularly to G-protein-coupled receptor
2. G protein releases GDP and binds GTP
3. Activated G protein activates adenyl cyclase
4. Adenyl cyclase converts ATP to cAMP
5. Cyclic AMP activates PKA
6. Phosphorylase kinase phosphorylates glycogen phosphorylase
7. Glycogenesis is promoted.
Activation of PKA
1. Cytosolic cAMP concentration increases
2. Two cAMP molecules bind to each PKA regulatory subunit
3. The regulatory subunits move out of the active sites of the catalytic subunits, and the R2C2 complex dissociates
4. The free catalytic subunits interact with proteins to phosphorylate Ser or Thr residues.
Identify events that contribute to the termination of a response in the GPCR, or 7TM receptor, pathway.
The receptor is inactivated by phosphorylation of Ser or other residues on its intracellular domain.
Gα hydrolyzes GTP to GDP and Pi.
The ligand dissociates from the receptor, which resumes its inactive conformation.
Which of the molecules are used as second messengers in signal transduction pathways?
IP3, cAMP, Ca ions, DAG, cGMP
cleavage of a membrane lipid to form compounds that ultimately cause the phosphorylation of specific proteins
PIP2 is hydrolyzed by PLC to produce IP3 and DAG. Then IP3 diffuses to the ER, where it causes the release of Ca ions, which activate PKC
Adenylate cyclase
converts ATP to cAMP
located in the membrane
Functions via nucleophilic attack by 3 OH on phosphorus attached to 5 OH of same nucleotide
play a role in signal transduction
Calmodulin
Activates upon Ca ions binding
Each calcium-binding domain in calmodulin is formed from a helix-loop-helix motif
A calcium ion is bound in the loop of an EF hand
steps of the insulin signaling pathway
1. Insulin is secreted
2. Binding of insulin to the alpha subunit of the insulin receptor
3. Activation of insulin receptor tyrosine kinase (RTK)
4. Phosphorylation of IRS proteins
5. Phosphorylation of PI3K
6. Conversion of PIP2 to PIP3
7. Activation of PIP3 dependent protein kinase B - PDK1
8. Acitvation of Akt
9. GLUT4 receptors transporters to cell membrane
tyrosine kinases (RTKs)
The intracellular domain has kinase domains.
A ligand binds to the extracellular domain.
RTKs are usually monomeric in the absence of a ligand.
The structure includes a transmembrane helix
GPCRs
7TM helices
Activate heterotrimeric G proteins directly
Eg: Epinephrine receptor
Phosphorylation of receptor can terminate signal or desensitize receptor
Ligand binding induces conformational changes in receptor
RTKs
Receptor activation causes phosphorylation of ts cytosolic subunits
Eg: Insulin receptor
Autophosphorylation of receptor can start signal
Ligand binding induces conformational changes in receptor
Proto-oncogenes
Code for proteins that usually promote cell division
Mutations that increase activity of these genes may lead to cancer
Tumor supressor genes
Mutations that decrease activity of these genes may lead to cancer
Some products of these genes normally function in repairing damaged DNA
Code for proteins that normally prevent uncontrolled cell division
Ras gene events
Specific transcription factors are activated by phosphorylation
Abnormally rapid cell growth and proliferation is induced
The ras proto-oncogene is converted into an oncogene
The three‑dimensional structure of the potassium channel has also revealed the presence of four K+‑binding sites in the constricted region. What forces potassium ions to exit the protein on the extracellular side of the membrane?
Binding of a second potassium ion to a site adjacent to the first potassium ion's binding site creates an electrostatic repulsion that helps to push the first potassium ion onto the next binding site
For charged species, what determines the free energy of ion gradients?
the electrochemical potential across the membrane
In passive transport, the energy that drives the movement of molecules across a membrane is provided by
the concentration gradient across the membrane
The Na+-K+ pump is an active transport system that
pumps sodium ions out of the cell and potassium ions into the cell
The three‑dimensional structure of the potassium channel provides a rationale for its selectivity.Which of the following is the basis for the ability of the potassium channel to discriminate between potassium and sodium ions?
The channel's constricted region allows for the potassium ion's hydration shell to be replaced by direct protein liganding, but the sodium ion is too small for this interaction to occur.
What channel opens in response to membrane depolarization?
voltage-gated
What must happen to the voltage‑gated sodium channel for the refractory period to end?
The ball domain is released from the channel pore, and the channel returns to the closed state.
In which structures are aquaporins found in high levels
kidneys and red blood cells
Acetylcholine receptors and sodium channels both allow sodium ions to pass through the membrane.What is the difference in how they are opened?
Acetylcholine receptors are ligand‑gated channels, whereas sodium channels are voltage‑gated.
Secondary transporters (or cotransporters) can be divided into symporters and antiporters.What is the basis for this distinction?
Symporters drive the movement of two molecules in the same direction, whereas antiporters drive the movement of two molecules in opposite directions.
What channel opens in response to binding of a particular molecule?
ligand-gated
Simple diffusion
Directly through the membrane
Oxygen
small non-polar molecules
facilitated diffusion
Via channel
Sodium
Large polar molecules
movement to area of lower concentration
Glucose transport into muscle cell
movement across a membrane
movement is assisted by proteins
Active transport
Requires energy
Sodium ions transport out of cell
movement across a membrane
movement is assisted by proteins
ABC transporters
Multidrug resistance protein eg. P-glycoprotein
2 ATP binding domains
Catalytic cycle begins with neither susbtrate nor ATP bound, with the transporter able to convert between closed and open forms
Substrate and ATP may be bound at the same time
ATP dependent
P-type ATPase transporters
An aspartate residue in the membrane pump is phosphorylated
sarcoplasmic reticulum Ca ion ATPase SERCA
Catylitic cycle begins with subtrate bound but ATP not bound eg. conformation of Ca ion
ATP dependent
Substrate and ATP may be bound at the same time
The sarcoplasmic reticulum calcium transport ATPase (SERCA) D351A mutant has the P domain Asp351 residue replaced by alanine. How would this affect the Ca2+ ATPase ?
SERCA D351A cannot have a stabilized E2 conformation, and is mostly present in one of the E1 (high Ca2+ affinity) conformations.

SERCA D351A is not able to be phosphorylated
Which structures are classified as carrier proteins?
Antiporters
Uniporters
Symporters
Which carrier proteins can mediate secondary active transport?
Symporters
Antiporters
propagation of a nerve impulse.
The influx of sodium ions makes the membrane potential more positive.

The action potential can only travel in one direction along the axon.

When voltage‑gated potassium channels open, potassium ions move out of the cell restoring the resting membrane potential.

The action potential triggers the opening of sodium channels further down the axon.

The action potential triggers the opening of voltage‑gated potassium channels.

The propagation of a nerve impulse relies on changes in membrane potential along the length of a nerve.
Ligand‑gated ion channels
Acetylcholine receptor
Change conformation in response to a signal molecule binding
form of passive transport
may participate in action potential
Voltage-gated channels
Change conformation in response to changing membrane potential
form of passive transport
may participate in action potential
What type of sugar is fructose?
Hexose
Formation of pyranose and furanose forms of a sugar generates a new asymmetric carbon.If the anomeric alcohol group in a cyclic sugar molecule is on the same side as the C‑6, the sugar is described as
(β)Beta anomer
Glucose yields a positive test with cupric ions, such as those of Fehling's solution, but sucrose does not because
glucose is in equilibrium with its free aldehyde form, whereas sucrose is not
Epimers
Differ at one of several asymmetric carbon atoms
D‑Glucose and L‑glucose are
Enantiomers
Glycoproteins are proteins to which carbohydrates have been covalently attached.The amino acid R groups that serve as sites for O‑linkages in glycoproteins include
hydroxyl‑containing R groups
Advanced glycation end products are
products of reactions between reducing sugars and free amino groups.
Human ABO blood groups are
the result of differing glycosyltransferase activities.
The furanose form of fructose is generated by formation of a hemiketal involving the attack of the C‑__ hydroxyl group on the C‑__ ketone.
5; 2
Once formed, the α and β forms of D‑glucose are
interconvertible only through a linear, open‑chain intermediate with which the cyclic forms are both in equilibrium
The processes of N-linked and O-linked glycosylation
oth take place in the Golgi apparatus
Glycoprotein
Conjugated with carbohydrates
Lysosomal enzyme
Lectin
Recognizes carbohydrates
Mannose 6-phosphate receptor
amino acids that attach carbohydrates to proteins
Serine, Threonine and Asparginine
Simple glycoproteins
often secreted
predominantly protein
Proteoglycans
Predominantly carbohydrates and contain glycosaminoglycan
play structural roles
Mucoproteins
Serve as lubricants
Predominantly carbohydrates and contain N-acetylgalactosamine
Which are possible components of glycosaminoglycans?
N‑acetylgalactosamine
negatively charged sulfate group
glycosaminoglycans
Chondroitin sulfate and keratan sulfate are examples of glycosaminoglycans

Glycosaminoglycans are heteropolysaccharides composed of repeating disaccharide units.
Why is cellulose not a source of nutrients for humans?
Vertebrate enzymes are unable to hydrolyze (β 1-4) linked glucose monomers
Humans, and most vertebrates, lack the enzyme cellulase
How many reducing ends are in one glycogen molecule?
1
The number of nonreducing ends in a glycogen molecule is _____ than
the number of reducing ends in the molecule
greater
Glycogen is an important fuel-storage form that is rapidly mobilized. Most glycogen metabolism takes place at the
nonreducing end
reducing sugars
The oxidation of a reducing sugar forms a carboxylic acid sugar
D‑Mannose (an aldose) is a reducing sugar
A disaccharide with its anomeric carbons joined by the glycosidic linkage cannot be a reducing sugar
fructose
hexose ketose
dihydroxyacetone
triose ketose
glyceraldehyde
triose aldose
Epimers
D-glucose and D-mannose
D-galactose and D-glucose
Anomers
alpha-D-glucose
beta-D-glucose
Aldose-ketose pair
D-glucose and D-fructose
D-ribose and D-ribulose
D-glyceraldehyde and dihydroxyacetone
Epimers, anomers, diastereomers
alpha-D-galactose and beta-D-galactose
Fatty acid
carboxylic acid with a long hydrocarbon tail that ranges from 3-30 carbon atoms
As the length of the hydrocarbon tail in the fatty acid _____, the melting point _____
Increases;increases
As the length of the hydrocarbon chain _____, the dispersion forces between adjacent molecules _______ and the melting point _______
Increases,increases, increases
Presence of a double bond in the hydrocarbon chain
decreases the melting point of a fatty acid
Unsaturated
double bonds
Saturated
no double bonds
What is the consequence of an unsaturated fatty acid having a double bond that is in a cis, rather than a trans, configuration?
There is a bend in the molecule.
Which of the properties is NOT a common property of all steroids?
found exclusively in animals
Which of the following is NOT a difference seen in archaeal membrane lipids relative to those of other organisms?
The central carbon of the glycerol backbone is not chiral
The most common way in which integral membrane proteins span the membrane is in
α helical segments.
Many lipid molecules are amphipathic, which means that
they have a dual nature with part of the molecule being hydrophobic and the other part hydrophilic
Of the three major types of membrane lipid, which is NOT found in prokaryotes?
cholesterol
The main use of hydropathy plots is to
identify membrane‑spanning helical regions in integral membrane proteins
Which two oxygen‑containing groups are esterified to the carboxyl groups of fatty acids to form a phosphoglyceride?
C‑1 and C‑2 hydroxyl groups of glycerol
cholesterol and its role in membrane fluidity
Cholesterol decreases membrane fluidity in areas called rafts, which contain large amounts of sphingolipids and cholesterol

Cholesterol increases membrane fluidity in a membrane that otherwise contains mostly long‑chain saturated fatty acids.
Membrane‑spanning α helix
Composed of about 20 hydrophobic residues
Membrane‑spanning β strands
Amino acid sequence pattern: nonpolar R group, polar R group (repeats)
Lipid‑anchored membrane protein
Often contains residues with covalently attached fatty acyl groups
Peripheral membrane protein
Can usually be released from membrane by concentrated salt solutions

membrane attachment depends upon electrostatic interactions with membrane phospholipid head groups
What is the effect of cholesterol in the cell membrane?
Cholesterol moderates membrane fluidity at low and high temperatures
Saturated
palmitic acid
stearic acid
monosaturated
oleic acid
polyunsaturated
linoleic acid
arachidonic acid
G proteins are converted from the GTP bound form to the GDP bound form by _____; they are converted from the GDP bound form to the GTP bound form by _____
nucleotide hydrolysis; nucleotide phosphorylation
Beta blockers are drugs that inhibit beta-adrenergic receptors and are used to control tachycardia (high heart rate) and anxiety disorders by countering the effects of epinephrine. Which of the following intracellular second messengers would be expected to decrease in a patient treated with a beta blocker?
cAMP
Caffeine prolongs and intensifies the effects of epinephrine. Which of the following potential mechanisms of action of caffeine is consistent with this effect?
inhibits cAMP phosphodiesterase, the enzyme that converts cAMP to AMP
The activation of the IP3/calcium system leads to growth stimulation in many cells, including cancer cells. In order to inhibit this second messenger system, you could try to develop a drug that
reacts chemically with the a-subunits of the Gaq proteins, thereby making them unable to activate phospholipase C
The treatment of cells with a membrane-permeant Ca2+ chelator (a sequestering agent) would inhibit the activity of which of the following kinases?
MAPK
A mutation of the SOS gene that results in a non-functional protein would have what effect on EGF signaling?
Ras could not be activated
The toxin produced by the intestinal bacterium Vibrio cholerae induces excessive diarrhea by stimulating the excretion of NaCl and large amounts of water into the intestine. The mechanism by which cholera toxin acts is ADP ribosylation of
the GTP-bound form of Gas, locking it in the active conformation
Which of the following is NOT true regarding P‑type ATPases?
Because of their common mechanism they lack specificity, and a given P‑type ATPase can transport different ions or molecules
The transport of an ion across a membrane against its concentration gradient can be accomplished by
the cotransport of another ion down its concentration gradient
Which of the following is NOT true of ion channels?
Ion channels are continually open, whereas pumps or secondary transporters depend on an energy source to open
The poison arrow frog, Phyllobates terribilis, produces a toxin called batrachotoxin, BTX. BTX blocks nerve signaling by binding to voltage‑gated sodium channels. If the voltage‑gated sodium channel still transports sodium after depolarization, which step does BTX likely block?
the voltage‑gated sodium channel's transition from the open to closed state
Hydropathy plot analysis of a protein of interest reveals a single, prominent hydrophobic peak. However, it is later discovered that this protein is soluble and not membrane associated. What may have caused the hydropathy plot to be misleading?
The protein contains a single α helix in its hydrophobic core
"Homeoviscous adaptation" is the process whereby bacteria adjust the fatty acid composition of their phospholipids to maintain constant membrane fluidity when incubated at nonstandard temperatures. Which of the following describes the lipid content of cells cultured at 30°C compared with control cells incubated at 23°C?
Fatty acids have fewer double bonds than those in control cells
Which of the following is an accurate statement regarding biological membrane lipids?
Plasma membrane glycolipids are preferentially located in the extracellular-facing leaflet of the lipid bilayer
Non reducing sugar
does not contain aldehyde or ketone groups for reduction.
Which of the following is an accurate statement regarding carbohydrates?
Glycogen and starch are both homopolymers of glucose
Which of the following best describes the mechanism by which the R subunit of PKA regulates the activity of the C subunit?
In the R2C2 complex, the active site of C is inaccessible to its protein substrates
A drug company is using recombinant DNA methods to prepare a modified α1‑antitrypsin that is more resistant to oxidation than the naturally occurring inhibitor. The drug company wants to target one internal amino acid in the inhibitor. Which single amino acid substitution should the drug company try to implement?
leucine in place of methionine
David comes into the emergency room late at night with a cut that will not stop bleeding. His mother, Rose, is worried that he has a bleeding disorder, just like his grandfather. The lab is closed, so the doctor cannot order a specialized coagulation test. However, the hospital does have a sample of blood from a classic hemophiliac. What is the simplest test the doctor could perform using David's blood to determine if it is missing factor VIII activity?
combine the samples and check for coagulation
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