Biochem Exam 3

Which of the following correctly describes the biochemistry of the amino acids at the termini of pepsin?

two nonpolar amino acids at the N-terminus and one polar amino acid at the C-terminus

An inhibitor that binds only to the ES complex and not free enzyme is known as a(n) ___________ inhibitor. radio_button_unchecked irreversible radio_button_unchecked mixed radio_button_unchecked uncompetitive radio_button_unchecked competitive SUBMIT

uncompetitive

Which of the following ligands is most likely to bind the receptor shown in B?

vitamin D

Along with other similar symptoms, both deficiencies can also result in reduced lactate levels during exercise. In order to distinguish between these two disorders, a physician could test the patient's lactate levels during exercise before and after administering glycerol. What would be the expected results if this test were performed?

-Lactate levels would be low after intense exercise and would not increase after glycerol was administered if the patient has a deficiency in lactate dehydrogenase. -Lactate levels would be low after intense exercise and would increase after glycerol was administered if the patient has a deficiency in muscle phosphofructokinase-1.

Structure-based drug design strategies often devise competitive inhibitors that bind to certain enzyme active sites. For example, saquinavir and indinavir are designed HIV protease inhibitors that bind to the aspartate protease enzyme of HIV, which is required for the virus to produce functional proteins for further HIV infection. Which of the following statements are true about saquinavir and indinavir?

-The removal of the phenyl ring (six-membered carbon ring containing three double bonds and no attached functional groups) on indinavir and saquinavir would likely affect their inhibitory activity. -D.Saquinavir and indinavir both have a component that mimics the natural Phe-Pro dipeptide substrate of aspartate protease. -Very high local concentrations of proteins with Phe-Pro or Tyr-Pro peptide bonds would reduce the effectiveness of saquinavir and indinavir in limiting HIV's infectivity of new cells.

The catalytic acitivity and/or conformational stability of this protein is likely dependent upon _____________of peripheral amino acid side chains. These side chains are expected to have a _________________value.

1) protonation 2) low pKa

Although the majority of ingested sucralose is not hydrolyzed in the small intestine, a small amount can be hydrolyzed to produce equimolar amounts of 1,6-dichloro-1,6-dideoxyfructose and 4-chloro-4-deoxygalactose. Are either of the hydrolysis products reducing sugars?

1,6-Dichloro-1,6-dideoxyfructose is a nonreducing sugar, and 4-chloro-4-deoxygalactose is a reducing sugar.

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. Determine which of the statements below accurately describe signal transduction pathways. Select the SIX correct statements.

1. A receptor changes conformation upon binding, transmitting a signal across the cell membrane. 2. Signal transduction cascades, often involving protein kinases, amplify a signal intracellularly. 4. A second messenger may carry a signal from the cell membrane to an organelle. 5. A ligand, such as a hormone, binds to a specific cell surface receptor on a target cell. 7. A receptor may pass on a signal by interacting with another protein or by acting as an enzyme. 8. Phosphatases remove phosphoryl groups from polypeptides, regulating a cell's response.

(A) Phosphorylation of glucose to produce glucose-6-phosphate has ΔG˚' = 13.8 kJ/mol without the use of ATP.(B) Coupling phosphorylation with ATP hydrolysis gives ΔG˚' = -16.7 kJ/mol.

13.8 -16.7

Which of the following best describes the relationship among a subunit of the protein, metal cofactors, and ligands?

A metal ion and ligand interact with the protein in locations proximal to one another.

What is the appropriate order of the following steps?A. Glutamine binding to uridylyltransferaseB. Adenylation of glutamine synthetaseC. Deuridylation of glutamine synthetase adenylyltransferase

A,C,B

Choose the correct statements about the function and activity of arrestin.

A. PKA phosphorylation also modifies GPCR, leading to arrestin binding to the receptor for endosomal transportD. Arrestin facilitates protein transport, which prevents a receptor from reassociating with the G protein complex

The figure below shows the activity curves of phosphofructokinase-1 (PFK-1) in the presence of allosteric regulators. Which allosteric regulator is responsible for curve C?

ATP

Which amino acid is NOT a target for kinases?

Asp

Put the following steps in the correct order describing inhibition of glutamine synthetase by a metabolite allosteric effector. A. Adenylation of glutamine synthetase. B. Glutamine binding to uridylyltransferase C. Deuridylation of glutamine synthetase adenylyltransferase

B,C,A

Why are Ras mutations so prevalent in certain types of cancers?

Because a dominant mutation in Ras requires only one mutation to be a gain of function oncogene activation

Once insulin has bound the α subunit of the insulin receptor, the β subunit of the receptor can bind to an insulin receptor substrate (IRS) protein, which acts as a membrane scaffold. What events happen next that enable the β subunit and the IRS protein to bind together?

Binding of insulin induces conformational changes in the β subunits, which enable them to autophosphorylate on tyrosine residues. These P-tyrosine residues are recognized by the phosphotyrosine binding sites (PTB domain) present in an IRS protein.

Both epinephrine (a tyrosine derivative) and glucagon (a peptide hormone) increase glucose export from the liver into the bloodstream. Each ligand binds a different receptor, but both lead to an activation of PKA. How does this happen?

Both receptors bind and activate the same Gα subunit, Gsα, which indirectly leadsto PKA activation.

Place the following steps describing receptor tyrosine kinase (RTK) signaling in proper order: A.phosphorylation of RTK cytoplasmic tails B.activation of downstream signaling pathways C.ligand binding, receptor dimerization, and kinase activation D.protein binding to RTK phosphotyrosines and phosphorylation of target proteins

C,A,D,B

Catabolic pathways are always paired with anabolic pathways. Why?

Catabolic pathways break down molecules and anabolic build up new molecules.

Below is shown the structure of a homodimer of the GR DNA-binding domain. Four areas are highlighted. Which is most likely to interact with DNA?

D

Put the following signal transduction pathway steps in the correct order: upstream signaling protein second messenger receptor protein first messenger target proteins downstream signaling protein

D,C,A,B,F,E

If protein kinase A is activated in a liver cell in response to glucagon binding to the 2-adrenergic receptor, which of the following will result?

Glycogen degradation will be turned on.

Whether a G alpha subunit is active or inactive depends on which guanine nucleotide is bound to it. Binding of GDP or GTP results in the protein switching between two conformational states. Which of the following answers best describes the structural changes that occur in a G alpha subunit due to guanine nucleotide binding?

Dissociation of GDP for GTP with the G alpha subunit structurally shifts the switch II helix region, allowing for the association of G alpha with its effector proteins, such as adenylate cyclase.

Which protein is part of the TNF receptor-activated programmed cell death signaling pathway? NFkB IKK TRAF2 FADD

FADD

Which one of the following processes occurs after activation of the PI-3K pathway by insulin signaling?

Glucose uptake rates Increase and lower blood glucose levels

How would the oxygen saturation of hemoglobin in an individual with bisphosphoglycerate mutase deficiency compare to that in an unaffected individual?

Hemoglobin oxygen saturation would be increased in the erythrocytes of individuals with bisphosphoglycerate mutase deficiency as compared to a normal individual.

Lactose intolerance is a condition caused by a deficiency in the lactase enzyme. Individuals with this deficiency can experience unpleasant symptoms if they eat lactose-containing foods such as dairy products. The human gene for lactase is expressed at high levels in infants to aid in the digestion of lactose in breast milk; however, lactase expression normally declines in adults, with the notable exception of people of Scandinavian descent.

Hydrolysis of lactose to produce glucose and galactose

Which of the following statements is true of procaspase 8? It is phosphorylated and activated by IKK. It is cleaved by TRADD and binds to p65. It is activated by auto-cleavage. It cleaves and activates procaspase 3.

It is activated by auto-cleavage

Which of the following is true of procaspase 8?

It is proteolytically inactive.

Mike has lactose intolerance and has to ingest commercial lactase in pill form before consuming milk products in order to avoid the unpleasant symptoms associated with this disorder. One day he noticed a classmate refusing a free sample of the new milkshakes sold in the campus cafe. His classmate, Jamal, explains that he has to avoid all milk products in his diet because he has galactosemia. Mike offers Jamal one of his lactase pills. Because both of their disorders are caused by consumption of milk products, he thinks Jamal should try lactase to see if it will allow him to try the milkshake. Should Jamal try the lactase pill to see if it will work?

Jamal should not follow Mike's advice. If Jamal ingests lactase along with the milkshake, it could cause harmful side effects.

Why does lactase deficiency lead to the retention of lactose within the small intestine and prevent transport across the intestinal lumen?

Lactose is a polar molecule and cannot cross the intestinal membrane without a transport protein. Transport proteins in the intestinal lumen are specific for monosaccharides.

Name the following disaccharide using the common name and the descriptive nomenclature.

Lactose: Gal(B1->4)Glc

One subtype of breast cancer involves the human epidermal growth factor receptor 2 gene (EGF receptor). One in every five breast cancers has a mutation in this gene. Understanding that this is a growth factor receptor gene, which of the answer choices best describes how this type of cancer develops?

Mutations that activate the kinase portion of the receptor result in a receptor that is constantly phosphorylated. This causes constitutive activation of downstream signaling and the resulting cell growth and proliferation.

Cultures of two different human cell types are exposed to the same steroid signaling molecule. Analysis of gene expression shows that only one of the cell types activated gene expression characteristic of the steroid signaling pathway. Which of the following is the most likely explanation for this difference? The steroid ligand can only cross the plasma membrane in one cell type. Only one cell type contains the DNA sequences that the steroid receptor binds to. Only one cell type phosphorylates the steroid ligand to activate it. Only one of the cell types expresses the cognate steroid receptor.

Only one of the cell types expresses the cognate steroid receptor.

A new protein is discovered that contains a pleckstrin homology domain. Which of the following is likely to bind to the protein?

PIP3

Which enzyme's activity is controlled by the levels of glucose-6-P and fructose-6-P in the cell?

Phosphoglucoisomerase

The spontaneous direction of a metabolic reaction is dictated by the ratio of substrate and products under equilibrium conditions (K) and under cellular conditions (Q). Compare the two reactions A→B and C→D. For A→B, ΔG˚ = -13 kJ/mol.For C→D, ΔG˚ = 3.5 kJ/mol.The cellular concentrations are as follows: [A] = 0.050 mM, [B] = 4.0 mM, [C] = 0.060 mM, and [D] = 0.010 mM. Which statement below correctly describes the relationship between Q and K for both reactions? Are these reactions spontaneous as written under cellular conditions?

Q < K for both reactions. Both are spontaneous at those concentrations of substrate and product.

Which of the following statements accurately describe receptor tyrosine kinases (RTKs)? Select the FOUR true statements.

RTK signaling always involves kinase activity. A ligand binds to the extracellular domain. RTKs are dimeric in the presence of ligand. Ligand binding is required for autophosphorylation (cross-phosphorylation).

Rosiglitazone is an antidiabetic drug meant to target adipose cells, enhancing insulin effects. The drug mimics the fatty acid metabolites that bind to a nuclear receptor found mostly in fat, liver, and a few other tissues.Cortisone is a type of glucocorticoid mimic that binds to a nuclear receptor, activating the receptor's transcriptional regulatory function. The ligand-activated receptor binds coregulatory proteins, and the protein complex targets gene transcription involved with inflammation.Which of the following statements about these two drugs best describe their mechanism of action?

Rosiglitazone will bind to its receptor (peroxisome proliferator-activated receptor), and the receptor-ligand complex can bind to the RXR receptor in a head-to-tail fashion. Receptor dimers with bound cortisone bind to the DNA target using a zinc finger to bind to an inverted repeat that must be at least partially palindromic to be recognized.

Below is shown a short sequence of a protein. Which of the following domains would most likely bind this sequence?

SH3

Which of the following is correct about the binding of epidermal growth factor to its receptor?

The cytoplasmic tail of EGFR2 is phosphorylated before EGFR1.

Observe the ribbon structure of pepsin. To do this, click the green-outlined box at the bottom of the player. Green x's will appear over your selection. Then go to the dropdown menu and on the "Display" line, click the "Toggle Ribbon for selection" icon. Then click the "Toggle CPK for selection" icon to remove the space-filling display. To remove the green x's, click "Clear Selection" on the "Misc" line of the dropdown menu. Determine the relative proportions of secondary and quaternary structure(s). What best describes these structures?

The major secondary structures are beta sheets, and there is no quaternary structure.

What characteristic is true for both RTKs and GPCRs?

The receptor undergoes a conformational change on activation.

An enzyme undergoes a mutation that causes it to lose the ability to be regulated via phosphorylation. Which of the following mutations may lead to this loss of regulation? Assume that the overall structure is not altered by the mutation.

Tyr --> Phe

An enzyme undergoes a mutation that causes it to lose the ability to be regulated via phosphorylation. Which of the following mutations may lead to this loss of regulation? Assume that the overall structure is not altered by the mutation.

Tyr-->Phe

Why would mutation of a tyrosine residue to glutamate in the intracellular portion of a growth factor receptor lead to increased tumor formation?

Unlike tyrosine, a glutamate will leave the receptor "constitutively" active and no longer responsive to the phosphatases that shut off such signaling. A receptor with a glutamate in place of a tyrosine is a "phosphomimetic." That is, the protein mimics the phosphorylated state of tyrosine.

You are culturing mammalian brain cells with standard growth media that includes 10% fetal bovine serum (FBS). FBS has a number of hormones and other components that stimulate cell growth. Over a busy weekend you made a mistake and left the cells in media without FBS. These cells have begun apoptosis while normally cultured cells are growing and surviving just fine.

Withdrawal of a positive growth signal induced the cell death pathway of TNF-alpha.

Using concentrations of intermediates found in a cell, the phosphorylation of glucose using inorganic phosphate has ΔG' = 19.7 kJ/mol, while phosphoryl transfer from ATP (ATP investment) results in ΔG' = -34.5 kJ/mol. What does this tell you about the values of Q and Keq for the phosphorylation of glucose with and without energy investment from ATP?

Without ATP investment, Q > Keq, and with ATP investment Q < Keq.

A ligand binds to a transmembrane protein. This causes a conformational change in the protein that is detected by an intracellular protein. The intracellular protein is an enzyme that adds phosphate groups to target proteins. The phosphorylated proteins cause a physiological change within the cell. This is an example of

a signal transduction pathway

Procathepsin B is a lysosomal protease that is first translated as a proenzyme. On autocleavage it is fully activated. Procathepsin B is

a zymogen.

The GS-alpha subunit of trimeric G proteins can function to

activate adenylate cyclase

If phosphofructokinase experienced a mutation that interfered with substrate binding, then what other enzyme is going to be most immediately impacted in terms of accessing substrate?

aldolase

which human disease states are treated by glucocorticoids based on the anti-inflammatory response of cells to glucocorticoid treatment? Choose the three most common (use a Google search).

arthritis, asthma, dermatitis

If a mutation occurred in SODD that prohibited its interaction with the DD of TNF receptor, the TNF receptor would

bind TRADD, even in the absence of TNF-.

Which of the following is not a biochemical process affecting the bioavailability of enzymes?

binding of a competitive inhibitor

Metabolism is best defined as a collection of enzymes that convert metabolites into pathways. biochemical reactions that convert mechanical work into energy. cellular processes that activate cell division. biochemical reactions that convert chemical energy into work.

biochemical reactions that convert chemical energy into work

Select only one of the four identical subunits of the protein by clicking one of the green-outlined boxes next to a subunit listed along the bottom of the player. When the subunit is selected, it will be covered with green x's.Next, change the display of the selected subunit to ribbon structure by clicking the dropdown menu in the upper right corner and then clicking "Toggle Ribbon for selection" on the Display line. Click "Toggle CPK for selection" to remove the space-filling display. To remove the green x's, click "Clear Selection" on the Misc line. Determine the secondary structure(s) that is/are exhibited in this polypeptide.

both alpha helices and beta sheets

The phosphoinositide-3 kinase (PI-3K) pathway is activated by insulin signaling in liver cells. Number the following statements 1-10 to order the sequence of events that lead to glucose uptake and glycogen synthesis in response to insulin signaling. The abbreviations for each signaling component of the pathway are defined in Section 8.3 of the textbook.

chegg

Which of the following list includes ONLY first messengers?

cortisol, insulin, prostaglandins

A __________ inhibitor is a type of irreversible inhibitor.

covalent

Consider the reaction shown below (A) Identify the kind of chemical catalysis (B) Identify which of the amino acids can act as X in the reaction Choose ONE correct answer for each (A and B).

covalent catalysis HIS

The Lineweaver-Burk plot shows data obtained for an enzyme in the absence and presence of a noncompetitive inhibitor. If the [I] is increased significantly in the experiment, the Vmaxapp would __________ and the Kmapp would __________.

decrease; stay the same

Which of the following first messengers is unique because it is not water soluble and does not bind directly to a membrane receptor?

estradiol

In the following series of reactions, what is the shared intermediate?

fructose -6-P

Glucose and fructose are both C6H12O6. What is the structural difference between them?

fructose is a five membered ring and glucose is a six membered ring

In which of the following glycolytic pathway reactions is ATP phosphoryl transfer energy required to drive the reaction in the forward direction? glucose → glucose-6-phosphate 1,3-Bisphosphoglycerate → 3-phosphoglycerate 2-Phosphoglycerate → 3-phosphoglycerate glucose-6-phosphate → fructose-6-phosphate

glucose → glucose-6-phosphate

Acetylcholinesterase is an important enzyme in the nervous system. Acetylcholinesterase activity is blocked by the nerve agent sarin gas, which forms a covalent bond with a Ser in the active site of the enzyme. Sarin gas is a(n)

irreversible inhibitor

An estrogen-dependent breast cancer cell line is grown in a medium that contains estrogen. Cell proliferation is monitored over time. In a separate experiment, the cell line is grown in a medium that lacks estrogen but includes bisphenol A, a compound found in polycarbonate plastics. When monitored, cell proliferation is higher than in the presence of estrogen. A possible explanation of these results is that bisphenol A

is an agonist of the estrogen receptor

Which of the following are characteristics of allosteric enzymes like ATCase? Choose the THREE that apply. Allosteric enzymes:

may have binding sites for regulatory molecules that are separate from active sites. interconvert between a more active form and less active form. tend to have a sigmoidal (S-shaped) curve of V0 vs. [S].

Cancer cells have many alterations in their metabolic pathways, including some that alter the way they metabolize and use glucose. This is known as the Warburg effect. One component of the Warburg effect is the inhibition of the enzyme that converts pyruvate to acetyl CoA. Under these conditions, what metabolite will be elevated in cancer cells as compared to noncancerous cells even under normal oxygen saturation?

lactate

Review the figure below. Shared intermediates are used so effectively in coupled reactions because they

limit product diffusion and allow intermediates to channel from one enzyme to the next.

How can an unfavorable reaction (∆G°' > 0) still occur in a metabolic pathway?

link it to a favorable reaction

Flux is defined as the rate at which __________is/are interconverted.

metabolites

Which enzyme is responsible for terminating the activity of membrane-bound PIP3?

phosphatase and tensin homolog, PTEN

Which kinase is the only one in the insulin receptor signaling pathway that phosphorylates a glycolipid rather than another kinase?

phosphatidylinositide 3-kinase (PI-3K)

Erythrocytes with a deficiency in both pyruvate kinase and bisphosphoglycerate mutase would have 2,3-bisphosphoglycerate levels similar to that of unaffected erythrocytes.

pyruvate kinase

A plot of vo versus [S] for aspartyl transcarbamoylase displays three sigmoidal lines. If the line in the middle represents the enzyme activity in the absence of any allosteric effectors, then the line to the __________ represents the enzyme in the __________ when bound to __________.

right; T state; CTP

Cyclic GMP is the __________ during vasodilation.

second messenger

While glucagon (a peptide) and epinephrine (a tyrosine derivative) are very different agonists, both signal through GPCR systems. Some of the components of the pathways are unique, while other signaling components are shared between both systems. Place each item in the appropriate category: glucagon and epinephrine shared, glucagon independent, or epinephrine independent.

shared: -camp signaling pathways -gsa activation -adenylate cyclase activation -net accumulation of glucose glucagon: -peptide binding to GPCR receptor Epinephrine: -Gqa activation -activation of phospholipase C -ligand binding to adrenergic receptor

Nuclear receptors bind as dimers to inverted repeat DNA sequences. These receptors can be categorized into two groups: steriod receptors and metabolite receptors. Match the description with the type of nuclear receptor.

steroid receptors: -bind to inverted base repeats due to the orientation of the receptor dimer -these receptors typically bind cholesterol-derived hormones -bind as head - to - head homodimers metabolite receptors: -bind to direct repeat DNA sequences -form head-to-tail dimers -ligands are often derived from dietary nutrients, including vitamins, lipids, and derivatives of amino acids

Muscle relaxation in response to neuronal stimualtion and nitric oxide signaling would be reduced if a(n) ______________was present.

stimulator of cGMP phosphodiesterase

For the following reaction A→ B, if at equilibrium > 0, what can be said about the directionality of the reaction?

strongly favored i the reverse direction

Let's get warmed up to revisit bioenergetics, which we covered in Module 1, and see if you can remember how equilibrium relates to spontaneity of a reaction written from left to right. In the reaction A→ B, what can be said about the directionality of the reaction if when starting with equal concentratios of A and B at time zero (T0), you find that at equilibrium 30 minutes (T30) later, that [B] >> [A]?

strongly favored in the forward direction

When protein kinase A (PKA) is inactive, which of the following is true?

the intrinisic pseudosubstrate peptide is bound to the active site

A hydrophobic environment is necessary for optimal activity of phosphoglycerate kinase

to prevent hydrolysis of 1,3-bisphosphoglycerate.

Glucokinase is important for the regulation of glycolysis because it

traps extra glucose in liver cells for glycogen production.