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medical sciences
biochemistry

Questions and Answers of Biochemistry

You are studying protein kinase A (PKA)-mediated cell signaling in a mammalian cell line, in which PKA levels are sensitive to two different hormones, XGF and YGF. Examine the results shown below and
The actions of caffeine, theobromine, and theophylline result in relative decreases in cAMP. Suggest a biochemical rationale based on the information given in Box 13-4.
Describe the intracellular signaling cascade mediated by phospholipase C activity. How is phospholipase C activated?
The insulin receptor can interact with several proteins. What are these proteins and what signaling pathways are they linked to?
Li+ ions inhibit the recycling of PIP2. Is Li+ likely to counteract or enhance the effects of phorbol-13-acetate?
How are SH2 and SH3 domains important in the activation of Ras by receptor tyrosine kinases?
How does the binding of ligand to a receptor tyrosine kinase lead to changes in gene expression?
How do scaffold proteins help to regulate signal transduction pathways?
Compare the overall structure and mode of signal transduction by G protein-coupled receptors and receptor tyrosine kinases.
During G protein activation, which subunit exchanges GDP for GTP? What is the immediate consequence of this exchange?
Aluminum fluoride (AlF3) has been widely used in studies of the molecular mechanism of G protein transformations between the GDP- and GTP-bound forms. Suggest why this inorganic compound has proved
Suggest three mechanisms by which the β-adrenergic signaling pathway utilizing the second messenger cAMP can be "turned off."
An insulin receptor substrate (IRS) contains a so-called plekstrin homology (PH) domain that binds to the inositol head group of membrane lipids, a phosphotyrosine-binding (PTB) domain that differs
Would the following alterations to Src be oncogenic? Explain. (a) The deletion or inactivation of the SH3 domain. (b) The mutation of Tyr 416 to Phe.
Would the following alterations to Src be oncogenic? Explain. (a) The mutation of Tyr 527 to Phe. (b) The replacement of Src residues 249 to 253 with the sequence APTMP.
Explain why a protein tyrosine phosphatase would include an SH2 domain in addition to its phosphatase domain.
Retroviruses bearing oncogenes will infect cells from their corresponding host animal but will usually not transform them to cancer cells. Yet, these retroviruses will readily transform immortalized
Trastuzumab (Herceptin; Section 7-3) is an antibody that binds to the extracellular domain of the growth factor receptor HER2. Explain why trastuzumab would be an effective treatment for cancer in
Mycobacterium tuberculosis is an intracellular bacterium that causes tuberculosis. The M. tuberculosis genome includes 17 genes encoding adenylate cyclase, whereas free-living bacteria typically have
Explain why mutations of the Arg residue in Gsα that is ADPribosylated by cholera toxin are oncogenic mutations.
Why doesn't cholera toxin cause cancer?
How does pertussis toxin inhibit phospholipase C?
Explain why activation of diacyglycerol kinase would limit signaling by the phosphoinositide pathway.
Lithium ion, which is used to treat bipolar disorder, interferes with the phosphoinositide signaling pathway by inhibiting enzymes such as inositol monophosphatase and inositol polyphosphate
The SHP-2 protein participates in insulin signaling through its indirect activation by the insulin receptor (Fig. 13-31), a receptor tyrosine kinase. Yet SHP-2 is a protein tyrosine phosphatase. Is
Estimate the binding affinity of a ligand for its receptor from the following data:
Calculate the binding affinity of a ligand for its receptor from the following data:
Hormone A binds to its receptor with a KL of 5 μM. In the presence of 2.5 μM compound B and 2.0 μM hormone A, 1.0 μM of A remains unbound. Calculate the binding affinity of B for the hormone
Propranolol binds to β-adrenergic receptors with a KI of 8.9 × 10-9 M. What concentration of propranolol would be required to achieve a 50% reduction in the binding of the receptor agonist
In searching for life on Mars in the 1970s, the Viking spacecraft tested the Martian soil for rapid oxidation-reduction reactions. Explain why such reactions might indicate the presence of life.
Using the curved-arrow convention, show the transfer of electrons in the reduction of pyruvate to lactate in the presence of NADH + H+.
In the diagram below, indicate the direction of flow of electrons and the voltage (on themeter) for the following half-reactions under standard conditions:Zn2+ + 2e- †’ Zn E° = -0.763
At pH 0, 1/2 O2 + 2H+ + 2e- ⇆ H2 O................E° = 1.23 V Is oxygen reduction more favored at pH 0 or at pH 7? Explain in electrochemical terms as well as in terms of chemical equilibria.
Consider the reaction in which acetoacetate is reduced by NADH to Î²-hydroxybutyrate:Calculate Î”G for this reaction at 25°C when [acetoacetate] and [NADH] are 0.01 M, and
Radioactive isotope tracers and metabolic inhibitors have been essential to the elucidation of metabolic pathways. Can both kinds of agents be used to determine the order of metabolites in a
Many biosynthetic pathways have been elucidated by the analysis of genetic mutations in organisms such as Neurospora crassa (a mold) and Escherichia coli. How would you elucidate the steps of a
You have isolated four mutants in amino acid metabolism of the mold N. crassa. Mutant 1 requires two compounds for growth, X and Z. Mutant 2 requires only X. Mutants 3 and 4 require only Z. Mutant 3
Evaluate the accuracy of the following two statements on the interpretation of DNA chip results such as those presented in Figures 14-18 and 14-19. (a) DNA chip data allow one to determine the number
Use the following terms to fill in the diagram below: ADP, Pi, NADP+, ATP, NADPH, carbohydrates, proteins, lipids, acetyl-CoA, catabolism, anabolism.
Phosphofructokinase (PFK) catalyzes the reaction ATP + fructose-6-phosphate (F6P) ⇆ fructose-1,6-bisphosphate (FBP) + ADP Explain why the reaction rate is relatively insensitive to changes in the
What processes maintain the cellular concentration of ATP?
Why don't "high-energy" compounds such as phosphoenolpyruvate and phosphocreatine (Figure 14-6) break down quickly under physiological conditions?
Explain how phosphocreatine acts as an ATP "buffer."
Many metabolic reactions are actually coupled reactions. A common coupled reaction is substrate phosphorylation by ATP. For example, the oxidation of glucose begins with its phosphorylation to
Aldolase catalyzes the reactionÎ”G°€² for this reaction is 22.8 kJ‹…mol-1. In the cell at 37°C, the Î”G for this reaction is -5.9
Cells carry out anabolic as well as catabolic pathways, with some enzymes functioning in both types of pathways. (a) Explain why these enzymes catalyze near-equilibrium reactions. (b) Explain why
The ∆G°' for hydrolytically removing a phosphoryl group from ATP is about twice as large as the ∆G°' for hydrolytically removing a phosphoryl group from AMP (-14 kJ ∙ mol-1). Explain the
The reaction catalyzed by malate dehydrogenase,has a ˆ†G°' = 4.6 kJ ˆ™ mol-1. (a) Would this reaction occur spontaneously in a cell? (b) How does the citrate synthase reaction
Predict whether creatine kinase will operate in the direction of ATP synthesis or phosphocreatine synthesis at 25°C when [ATP] = 4 mM, [ADP] = 0.15 mM, [phosphocreatine] = 2.5 mM, and [creatine] = 1
If intracellular [ATP] = 5 mM, [ADP] = 0.5 mM, and [Pi] = 1.0 mM, calculate the concentration of AMP at pH 7 and 25°C under the condition that the adenylate kinase reaction is at equilibrium.
List the following substances in order of their increasing oxidizing power: (a) Acetoacetate, (b) Cytochrome b (Fe3+), (c) NAD+ (d) SO24-, and (e) Pyruvate.
Methanogens are prokaryotes that produce methane according to the net equationSome bacteria consume methane according to the net equation (a) Classify these two types of bacteria as autotrophic or
Is the reduced form of cytochrome c more likely to give up its electron to oxidized cytochrome a or cytochrome b?
Aerobic organisms transfer electrons from reduced fuel molecules to O2, forming H2O. Some anaerobic organisms use nitrate (NO3-) as an acceptor for electrons from reduced fuel molecules. Use the
Under standard conditions, will the following reaction proceed spontaneously as written?
Under standard conditions, will the following reaction proceed spontaneously as written?
Write a balanced equation for the oxidation of ubiquinol by cytochrome c. Calculate ∆G°' and for the recation.
Under standard conditions, is the oxidation of free FADH2 by ubiquinone sufficiently exergonic to drive the synthesis of ATP?
A hypothetical three-step metabolic pathway consists of intermediates W, X, Y, and Z and enzymes A, B, and C. Deduce the order of the enzymatic steps in the pathway from the following information: 1.
Would gene chips containing bacterial DNA segments be useful for monitoring gene expression in a mammalian cell?
Why do DNA chips often contain segments derived from cDNA rather than genomic DNA segments?
Citrate synthase catalyzes the reactionThe standard free energy change for the reaction is -31.5 kJ ˆ™ mol-1. (a) Calculate the equilibrium constant for this reaction at 37°C. (b) Would
A certain metabolic reaction takes the form A → B. Its standard free energy change is 7.5 kJ ∙ mol-1. (a) Calculate the equilibrium constant for the reaction at 25°C. (b) Calculate ∆G at 37°C
Describe the two-stage "chemical strategy" of glycolysis and write a balanced equation for each phase.
Fluoride ions specifically inhibit enolase in the presence of Pi in cell extracts. (a) Explain why both 2PG and 3PG accumulate in the presence of F- and Pi. (b) Explain why 1,3-BPG does not
How does a muscle cell maintain the [NAD+]/[NADH] ratio during the catabolic breakdown of glucose?
Compare the rates of ATP production in fermentation versus oxidative phosphorylation. Which process is utilized in rapid bursts of muscular activity?
In many metabolic pathways the first reaction is the rate-determining step of the pathway. (a) What is the rate-determining step of glycolysis? (b) What rationale can you offer for this "unusual"
Some organisms use glycerol as a carbon energy source, and it is also an intermediate in fructose metabolism. (a) Write equations for the reactions required to oxidize glycerol to pyruvate. (b)
The diagram below shows the interconversions of the nonoxidative reactions of the pentose phosphate pathway.(a) Which sugar phosphates correspond to the 5C compounds? (b) Which sugar phosphate
The nonoxidative reactions of the pentose phosphate pathway convert pentose phosphates into hexose phosphates. (a) For every 3 glucose phosphates that enter the pentose phosphate pathway, how many
Ribulose-5-phosphate is converted to xylulose-5-phosphate and ribose-5-phosphate by an epimerase and an isomerase, respectively. What distinguishes these isomerizations?
You obtain a mutant transketolase from yeast that binds R5P and E4P poorly. What unique side product of the reaction catalyzed by this enzyme might you find in these cells?
The conversion of G6P to R5P via the reactions of glycolysis and the pentose phosphate pathway, without the production of NADPH, can be summarized asWhat reaction requires ATP? How do you account for
Examine the following five glycolytic intermediates:(a) Name each intermediate. (b) Write the order in which they appear in glycolysis. (c) Which intermediate is a reactant in substrate-level
For the reaction catalyzed by triose phosphate isomerase, what is the equilibrium ratio of reactants and products under standard biochemical conditions? How does this ratio differ from the ratio
How does the GAPDH-catalyzed exchange of 32P between Pi and 1,3-bisphosphoglycerate corroborate the existence of an acyl-enzyme intermediate in the GAPDH reaction?
2,3-BPG is an intermediate in the reaction catalyzed by phosphoglycerate mutase. Why does the cell require trace amounts of 2,3-BPG?
If the cytosolic [NAD+]/[NADH] ratio is 100 and the [ATP]/[ADP][Pi] ratio is 10, what is the actual (not equilibrium) ratio of [GAP]/[3PG] at 37°C in the cell? Assume that [H+] =1, its value in the
Which of the 10 reactions of glycolysis are (a) Phosphorylations, (b) Isomerizations, (c) Oxidation-reductions, (d) Dehydrations, and (e) Carbon-carbon bond cleavages?
The half-reactions involved in the lactate dehydrogenase (LDH) reaction and their standard reduction potentials areCalculate (G at pH 7.0 for the LDH-catalyzed reduction of pyruvate under the
(G(( for the aldolase reaction is 22.8 kJ . mol-1. In the cell at 37(C, [DHAP] / [GAP] = 5.5. Calculate the equilibrium ratio of [FBP] / [GAP] when [GAP] = 10-4 M.
The catalytic behavior of liver and brain phosphofructokinase-1 (PFK-1) was observed in the presence of AMP, Pi, and fructose- 2,6-bisphosphate. The following table lists the concentrations of each
What is the advantage of activating pyruvate kinase with fructose- 1,6-bisphosphate?
Consider the pathway for catabolizing galactose. What are the potential control points for this pathway?
Yeast take up and metabolize galactose, using the pathway outlined in Fig. 15-28. Galactose-1-phosphate, an intermediate of this pathway, inhibits phosphoglucomutase. Can this explain why galactose
(a) Describe how glycerol enters the glycolytic pathway. (b) What is the ATP yield for the conversion of glycerol to pyruvate?
When the pathogen Salmonella typhimurium infects mammalian cells, the host cell protease caspase-1 is enabled to cleave and thereby activate signaling proteins that instigate the immune response. The
Some organisms can anaerobically convert glycerol to pyruvate. Could homolactic or alcoholic fermentation regenerate sufficient NAD+ to support this pathway?
Draw the enediolate intermediate of the ribulose-5-phosphate isomerase reaction (Ru5P ( R5P).
Draw the enediolate intermediate of the ribulose-5-phosphate epimerase reaction (Ru5P ( Xu5P).
Describe the products of the transketolase reaction when the substrates are a five-carbon aldose and a six-carbon ketose. Does it matter which of the substrates binds to the enzyme first?
Some bacteria catabolize glucose by the Entner-Doudoroff pathway, a variant of glycolysis in which glucose-6-phosphate is converted to 6-phosphogluconate (as in the pentose phosphate pathway) and
The aldolase reaction can proceed in reverse as an enzymatic aldol condensation. If the enzyme were not stereospecific, how many different products would be obtained?
Bacterial aldolase does not form a Schiff base with the substrate. Instead, it has a divalent Zn2+ ion in the active site. How does the ion facilitate the aldolase reaction?
Arsenate (AsO), a structural analog of phosphate, can act as a substrate for any reaction in which phosphate is a substrate. Arsenate esters, unlike phosphate esters, are kinetically as well as
The enzyme phosphoglucomutase interconverts glucose-1-phosphate and glucose-6-phosphate. Why is this enzyme likely to include a side chain such as Ser in its active site?
The compound you identified in Problem 7 is a metabolic regulator. Predict its effect on (a) hexokinase and (b) PFK.
The pyruvate ( lactate reaction in animals is reversible, but the pyruvate ( ethanol fermentation in yeast is irreversible. Explain.
Below is a diagram showing the synthesis and breakdown of glycogen [(glucose)]. Fill in the blanks and identify the enzyme that catalyzes each numbered reaction.

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