Biochemistry - Quiz 4
The KM of glucose 6-phosphate dehydrogenase for NADP+ is _____ the KM for NAD+.
1000 times lower than
How many phases are in the pentose phosphate pathway?
2
How many molecules of ATP and NADPH are consumed in the incorporation of a single CO2 molecule into a hexose?
3 ATP, 2 NADPH
How many ATP molecules are required by the C4 pathway for each hexose that is produced from CO2?
30
In the oxidative phase of the pentose phosphate pathway, transformation of 6-phosphogluconate to ribulose 5-phosphate is catalyzed by:
6-phosphogluconate dehydrogenase.
Drug candidate IC50(nmol) log(P) Cmax (μM) Bioavailability A 0.4 4.67 <0.1 B 0.01 3.70 <0.1 C 0.3 3.69 0.7 D 0.6 2.92 11 Consider the information concerning a related class of potential drugs in the table. Which one is the LEAST soluble in water and MOST hydrophobic?
A
In the overall equation for the Calvin cycle, three molecules of _____ and two molecules of _____ are consumed in incorporating a single CO2 molecule into a hexose.
ATP; NADPH
What pathway does NOT require extra energy to pump CO2 into the bundle sheath cells and is used by plants that are not able to grow in hot, dry climates?
C3 Pathway
What pathway ensures that sufficient amounts of CO2 are available?
C4 Pathway
Which of the following reactions catalyzed by transketolase does NOT coordinate the pentose phosphate pathway with glycolysis?
C5 + C6 C2 + C9; equal either 10 or 9
The source of carbon for the Calvin cycle is:
CO2
Why is the C4 pathway necessary for tropical plants?
Carbon dioxide is concentrated in bundle-sheath cells, which are the major sites of photosynthesis.
Which abbreviation is used for the concentration of a substance required to achieve 50% of the maximal response in biological assays using living cells or tissues?
EC50
Which statement for the enterohepatic cycling process is FALSE?
Enterohepatic cycling is useful for the blood-brain barrier. TRUE: Some drugs can move from the blood circulation to the liver. Xenobiotics can be actively transported into bile and after concentrating in the gallbladder get into the intestine. Enterohepatic cycling can decrease the rate of excretion of xenobiotics because they escape from an excretory pathway and reenter the circulation. In the intestine, the drugs and metabolites can be excreted through the stool, reabsorbed into the bloodstream, or further degraded by digestive enzymes.
What prosthetic group or enzyme does NOT take part in photorespiratory reactions?
FAD; BUT DOES: glycolate oxidase catalase transaminase FMN
What statement is CORRECT in uncomplicated cases of titration of a receptor with a ligand when the ligand concentration equals the dissociation constant?
Half of the receptors are bound to the ligand.
INCORRECT statement about an enzyme competitive inhibitor's study.
IC50 is higher when the concentration of the natural substrate is lower. CORRECT statement: IC50 depends on the Michaelis constant for the normal substrate, KM. IC50 depends on the concentration of the normal substrate. IC50 is higher when the concentration of the natural substrate is higher. IC50 is higher when the Michaelis constant for the normal substrate, KM, is lower.
Which statement about penicillin is FALSE?
In 1928, Alexander Fleming observed that colonies of the bacterium Staphylococcus aureus changed color when they were adjacent to colonies of the mold Penicillium notatum (THEY WOULD DIE); TRUE: Alexander Fleming realized that mold produced a substance that could kill disease-causing bacteria. An industrial process was developed for the production of penicillin from Penicillium mold on a large scale. The availability of synthetic penicillin derivatives opened the way for scientists to explore the relations between structure and function. A four-membered β-lactam ring is the key to the antibacterial action of penicillin.
What feature is NOT related to pathogen genomics?
Knockout allows drug developers to evaluate potential targets without any preconceived notions regarding pathogenic activities. TRUE: Genomes of different species can be compared to find proteins essential for cell survival that are conserved in a wide range of strains. It is possible to get a complete sequence of different strains to identify the unique targets essential for pathogenic activity. Pathogen genomics is a useful tool for the discovery of new antibiotics. Genomes of hundreds of pathogens have now been sequenced.
Which statement about thiopurine methyltransferase is FALSE?
Methylated thiopurines are often more active than parent compounds. TRUE: Mutations in the gene coding for it cause toxicity of thiopurine drugs at doses that are well tolerated by most patients. It is a xenobiotic-metabolizing enzyme. Thiopurine methyltransferase adds a methyl group to sulfur atoms of thiopurine compounds. Patients with rare variant alleles express the variant enzymes that are less stable.
Statement that is FALSE about genomic analyses that can aid in drug discovery.
Millions of compounds can be tested in high-throughput screening. TRUE: Novel proteins that are not part of families already supplying drug targets can be identified through the use of genomic information. Potential targets can be identified in the human proteome. Mouse studies provide drug developers with a powerful tool: the ability to disrupt specific genes in the mouse. Potential targets can be identified in the genomes of pathogens.
Which statement related to drug resistance of cancer is NOT correct?
Multiple drugs are not administered simultaneously in the same course of chemotherapy because cancer cells evolve multidrug resistance readily. IS CORRECT: Cancer cells can evolve drug resistance by overexpressing normal human proteins. Cancer cells may accumulate genetic changes that mitigate the effects of drugs. Cancer cells can mutate more quickly than normal. Cancer cells can evolve drug resistance by modifying proteins responsible for the cancer phenotype.
Which coenzyme is required by glyceraldehyde 3-phosphate dehydrogenase in chloroplasts to convert 3-phosphoglycerate into glyceraldehyde 3-phosphate?
NADPH
Which cofactor supplies the reducing power for reduction of glutathione by glutathione reductase?
NADPH
What process is wasteful because of conversion of organic carbon into CO2 without the production of ATP, NADPH, or another energy-rich metabolite?
Photorespiration
What statement is NOT included in the list of Lipinski's rules?
Poor absorption is more likely when the substance tends to aggregate at pH below 5. Lipinski's Rules: Poor absorption is more likely when the molecular weight is greater than 500 daltons. Poor absorption is more likely when the number of hydrogen-bond donors is greater than 5. Poor absorption is more likely when the number of hydrogen-bond acceptors is greater than 10. Poor absorption is more likely when the partition coefficient, log(P), is greater than 5.
FALSE statement concerning the activation of Calvin cycle enzymes
Reduced thioredoxin activates several degradative enzymes; TRUE: Reduced ferredoxin activates thioredoxin by ferredoxin-thioredoxin reductase. -The reduced form of thioredoxin activates many biosynthetic enzymes, including chloroplast ATP synthase, by reducing disulfide bridges that control their activity -NADPH is a signal molecule that activates two biosynthetic enzymes, phosphoribulokinase and glyceraldehyde 3-phosphate dehydrogenase. -In the dark, phosphoribulokinase and glyceraldehyde 3-phosphate dehydrogenase are inhibited by association with a protein called CP12.
Which statement about bacterial resistance to antibiotics is NOT correct?
Resistance often evolves when antibiotics are administered during a long period of time at high bactericidal doses. IS CORRECT: An individual microorganism may, by chance, have a minute genetic variation that makes it more suitable for growth and reproduction in the presence of the drug. The enzymes that degrade drugs are often encoded in plasmids, small circular pieces of DNA often carried by bacteria. Pathogens can raise enzymes that inactivate or degrade specific antibiotics. An affected person contains many bacterial cells that can mutate and reproduce mutations.
What is the main disadvantage of using knockout mice in drug discovery?
Testing drugs on animals reveals ethical problems.
CORRECT concerning the dissociation constant, Kd, of a drug X?
The Kd can be determined from the simple saturation curve of a binding reaction.
First attempts to develop cholesterol-lowering drugs targeted the later steps in cholesterol biosynthesis. Why did this strategy have to be abandoned?
The accumulation of an insoluble substrate caused cataracts and other deleterious side effects.
Which statement about aspirin is FALSE?
The acetyl group in aspirin is transferred to the active site of the hydroxylase component of prostaglandin H2 synthase and therefore blocks the active site. TRUE: A mixture called salicin was isolated from willow bark. Each year, approximately 35,000 tons of aspirin are taken worldwide. Felix Hoffmann developed a less irritating derivative of salicylic acid by treating it with a base and acetyl chloride. Even Hippocrates noted the use of extracts from the bark and leaves of the willow tree for pain relief.
What statement about the oxidation of drug compounds is FALSE?
The oxidation reactions are often referred to as phase II transformations of xenobiotic compounds. TRUE: The oxidation reaction often precedes conjugation. The oxidation reaction can generate modifications to which other groups such as glucuronic acid can be attached. The oxidation reactions take place primarily in the liver. The oxidation reactions often start before the drug ever reaches the maximal blood level.
Choose an example of mechanism-based or on-target toxicity.
The presence of too much of the anticoagulant drug coumadin can result in dangerous, uncontrolled bleeding.
What is the therapeutic index?
The ratio of the dose of a compound that is required to kill one-half of the animals, LD50, to a comparable measure of the effective dose, usually EC50
FALSE statement concerning the regulation of the pentose phosphate pathway.
The reaction of dehydrogenation of glucose 6-phosphate does not influence the rate of the whole pathway. TRUE: The level of NADP+ is very important in regulation of the pathway. Low levels of NADP+ inhibit oxidation of glucose 6-phosphate. NADPH competes with NADP+ in the binding active site of glucose 6-phosphate dehydrogenase. The nonoxidative phase of the pathway is primarily controlled by the availability of the substrates.
What statement for phase III clinical trials is NOT correct?
The trials are conducted to determine effective doses of the drug candidate. IS CORRECT: The efficacy of the drug candidate is tested on a large and diverse population. This phase is intended to detect side effects that may develop in a small percentage of the subjects who receive treatment. The trials are controlled and double-blinded. Subjects in the control group are given either a placebo or the best standard treatment available.
_____ is involved in both in the Calvin cycle and the pentose phosphate pathway.
Transaldolase
CORRECT statement concerning the action of transketolase and transaldolase.
Transaldolase transfers a three-carbon unit.
What compound is increased by the action of sildenafil (Viagra)?
cGMP
Rubisco:
catalyzes a deleterious oxygenase reaction.
What drug was discovered with the aid of structure-function studies (namely X-ray crystallography)?
celecoxib
Which approach is NOT used in structure-based drug design?
combinatorial chemistry of drug candidates. IS USED: molecular modeling of the shape and electronic structure of drug candidates evaluating ADME characteristics of the drug candidates X-ray crystallographic analysis of the target protein searching for structure-activity relationships
What metabolic adaptation is employed by plants living in hot, dry climates to prevent water loss and decrease photorespiration?
crassulacean acid metabolism
What enzymes is associated with the inflammatory response?
cyclooxygenase 2
In what part of the cell does the pentose phosphate pathway occur?
cytoplasm
Novel proteins that are not part of families already supplying drug targets can be identified through the use of genomic information. What is NOT suitable as a general way to identify them?
determining protein localization within the cell compartments of healthy organisms; SUITABLE: determining protein localization changes in diseased individuals determining tissues or cell types in which particular genes are expressed determining changes in expression patterns of cells from disease-afflicted organisms determining changes in posttranslational modifications in cells from diseased organisms
In clinical studies, participants with two variant alleles of the gene encoding the β1-adrenergic receptor:
did not respond well to metoprolol
What is the measure of the binding tendency of a ligand to its target?
dissociation constant
Process that is included in ADME properties.
drug metabolism
What substance does CO2 condense with to produce two molecules of 3-phosphoglycerate at the first step of the Calvin cycle?
enediolate intermediate
The products in the reaction of glyceraldehyde 3-phosphate plus sedoheptulose 7-phosphate are erythrose 4-phosphate and _______.
fructose 6-phosphate
What substance is a member of the hexose monophosphate pool?
fructose 6-phosphate
Dehydrogenation of glucose 6-phosphate at carbon 1 at the first step of the oxidative phase of the pentose phosphate pathway is catalyzed by
glucose 6-phosphate dehydrogenase
Falciparum malaria, a disease that requires NADPH for growth, is caused by the parasite Plasmodium falciparum. The deficiency of which enzyme leads to an increase NADPH, and eventually hemolytic anemia?
glucose 6-phosphate dehydrogenase
What enzymes do NOT take part in the regeneration of ribulose 1,5-bisphosphate?
glucose 6-phosphate dehydrogenase
In the oxidative phase of the pentose phosphate pathway, transformation of glucose 6-phosphate to 6-phosphoglucono-δ-lactone is catalyzed by:
glucose 6-phosphate dehydrogenase.
What is NOT the name of the pathway that oxidizes glucose to carbon dioxide to generate NADPH?
glucose phosphate pathway; CAN be called: pentose phosphate pathway hexose monophosphate pathway phosphogluconate pathway pentose shunt
What is conjugated to drugs to aid in their excretion?
glucuronic acid
What thiol-containing molecule in its reduced state is critical to reducing reactive oxygen species?
glutathione
Select all that apply. The products of the first reaction linking the pentose phosphate pathway and glycolysis are:
glyceraldehyde 3-phosphate. sedoheptulose 7-phosphate
Several variants of the gene coding for the β1-adrenergic receptor are common in the U.S. population. What is the difference between the alleles?
glycine replaces residue at position 49 or 389
What type of bond is used to link a glucuronic acid group to a xenobiotic?
glyosidic
The Schiff base:
has the structure R3C-NR'R"
In mice, a disruption of the gene for the α subunit of H+-K+ ATPase has resulted in the development of:
high gastric pH
What method of combinatorial chemistry begins by dividing the starting scaffold that is bound to beads into a number of sets?
high-throughput screening
What type of reaction is typically catalyzed by liver cytochrome P450?
hydroxylation
Which processes increases the effective concentration of a drug at the target site?
inactivation of metabolic pathways in the liver
What concentration change does NOT contribute to activation of Calvin cycle enzymes?
increase in the H+ concentration in stroma in the light reactions; DOES CONTRIBUTE: increase in the concentration of stromal NADPH in the light reactions. increase in the concentration of reduced ferredoxin in stroma in the light reactions. increase in the concentration of Mg2+ in stroma in the light reactions. increase in stromal pH in the light reactions.
A compound that binds to the receptors for the neurotransmitter dopamine and blocks them has potential use as a drug that:
increases dopamine and can be used to treat schizophrenia.
In the oxidative phase of the pentose phosphate pathway, transformation of 6-phosphoglucono-δ-lactone to 6-phosphogluconate is catalyzed by:
lactonase
What term describes a molecule that binds to a target molecule?
ligand
What drug was discovered by screening natural compound libraries?
lovastatin
Choose the case in which drug resistance may develop over the time of drug usage.
melanoma
What is a powerful animal model used for drug development?
mouse strains with specific genes knocked out
Which is NOT tested in clinical studies?
oral bioavailability of the drug candidate; IS tested: potential side effects of the drug candidate the efficacy of the drug candidate in a small number of persons the drug's safety on a large and diverse population doses that appear to be effective but are free of serious side effects
In what organelle does glycolate transform into glycine during photorespiration?
peroxisome
In which phase of drug development do healthy volunteers take the drug for initial safety studies?
phase I trials
Select all that apply. The formation of xylulose 5-phosphate from ribose 5-phosphate is catalyzed by:
phosphopentose isomerase. hosphopentose epimerase.
Which method is the most challenging when used in structure-based drug design?
prediction of the structure that will best fit into a binding site
Which form of thioredoxin activates certain Calvin cycle enzymes?
reduced
A cyclooxygenase inhibitor that is specific for COX2 has potential use as a drug that:
reduces inflammation and can be used to treat arthritis.
A compound that inhibits the action of histamine at the histamine H2 receptors in gastric parietal cells has potential use as a drug that:
reduces stomach acid production and can be used to treat ulcers
Which sugar(s) is/are converted into ribulose 5-phosphate by a single enzymatic step? Select all that apply.
ribose 5-phosphate xylulose 5-phosphate
What drug was discovered by screening libraries of synthetic compounds?
rosuvastatin
What is the name of the enzyme that is located on the stromal surface of the thylakoid membranes and catalyzes condensation of CO2 with the enediolate intermediate?
rubisco
What enzyme uses ATP to induce structural changes in rubisco and thus coordinates rubisco activity with the light reactions?
rubisco activase
What is NOT commonly conjugated to xenobiotic compounds?
salicylic acid; COMMONLY CONJUGATED: glucuronic acid sulfate group glutathione glutamate
What is shared by two paths to early drug discovery?
screening of a compound library, from which hits can be optimized into drug candidates
Which tissue has the least active pentose phosphate pathway?
skeletal muscle
In what part of the cell does the Calvin-Benson cycle occur?
stroma of the chloroplasts
A readily mobilized sugar that is commonly used to transport carbohydrates through a plant is:
sucrose
Which is NOT an additional function of the pentose phosphate pathway?
synthesis of hexose sugars for nucleotide biosynthesis. BUT CAN BE: catabolism of pentose sugars from the diet. synthesis of pentose sugars for nucleotide biosynthesis. catabolism of less common four- and seven-carbon sugars. synthesis of less common four- and seven-carbon sugars
What step distinguishes a target-based screening from a phenotypic one?
target validation
In the transketolase reaction:
the first step is the ionization of thiamine pyrophosphate.
In the transaldolase reaction:
the nitrogen atom of the protonated Schiff base plays the same role in transaldolase as the thiazole-ring nitrogen atom does in transketolase.
What prosthetic group is tightly bound to the enzyme transketolase?
thiamine pyrophosphate
_____ plays a major role in the regeneration of ribulose 1,5-bisphosphate
transketolase and aldolase
The donor of the two-carbon unit in the first reaction linking the pentose phosphate pathway and glycolysis is:
xylulose 5-phosphate
What enzyme is responsible for bacterial resistance to penicillin?
β-lactamase
