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medical sciences
biochemistry
Fundamentals of biochemistry Life at the Molecular Level 4th edition Donald Voet, Judith G. Voet, Charlotte W. Pratt - Solutions
Would intrinsically disordered polypeptide segments contain relatively more hydrophilic or hydrophobic residues? Explain.
It is often stated that proteins are quite large compared to the molecules they bind. However, what constitutes a large number depends on your point of view. Calculate the ratio of the volume of a hemoglobin molecule (65 kD) to that of the four O2 molecules that it binds and the ratio of the volume
In prokaryotes, the error rate in protein synthesis may be as high as 5 × 10-4 per codon. What fraction of polypeptides containing (a) 500 residues or (b) 2000 residues would you expect to contain at least one amino acid substitution?
Protein denaturation can be triggered by a variety of environmental insults, including high temperature, covalent modification, and oxidation. Explain why researchers have observed a correlation between the level of heat shock proteins and the ratio of oxidized to reduced glutathione in cells
Researchers introduced prions into normal mice and mice that were genetically predisposed to develop a disease resembling Alzheimer's. Explain why the Alzheimer's-prone mice displayed symptoms of the prion disease much sooner than did the normal mice.
The genetically engineered proteins that accumulate in bacterial inclusion bodies (Fig. 5-2) form amyloid structures. Such proteins are often difficult to recover in functional form from the bacteria. Explain.
Hydrophobic residues usually appear at the first and fourth positions in the seven-residue repeats of polypeptides that form coiled coils. (a) Why do polar or charged residues usually appear in the remaining five positions? (b) Why is the sequence Ile-Gln-Glu-Val-Glu-Arg-Asp more likely than the
Describe the primary, secondary, tertiary, and quaternary structures of collagen.
Match the descriptions on the left with the terms on the right.
Describe how BPG decreases the O2-binding affinity of hemoglobin in terms of the T ↔ R equilibrium.
How many conformational states are possible for a trimeric binding protein, whose three subunits each contain a ligand-binding site, when binding follows the (a) symmetry model or (b) the sequential model of allosterism?
Examine the hemoglobin variants in Table 7-1 and provide plausible answers to the following questions. (a) Which variant might be advantageous for an individual living in the Andes? (b) Which variants are likely to be the least stable, resulting in hemolytic anemia? (c) Which variants are likely to
Some hemoglobin S individuals have significant levels of fetal hemoglobin in their erythrocytes. Why is this an advantage?
Describe how ATP hydrolysis is involved in muscle contraction.
How does calcium regulate muscle contraction?
The graph below, the time course of microfilament polymerization in vitro, shows three phases of growth.(a) Describe the biochemical events taking place during each phase. Assume that ATP is in excess.(b) How might this graph look if ATP concentration becomes limiting as ATP is hydrolyzed by actin?
The heme moiety by itself can bind oxygen. What physiological function does the globin serve?
Indicate which class of immunoglobulin (IgA, IgD, IgE, IgG, or IgM) best corresponds to each characteristic listed below (more than one may be implicated by each description). (a) First to be secreted in response to an antigen (b) Implicated in allergic reactions (c) Occurs in the intestinal
The following questions refer to the production of monoclonal antibodies. (a) Why are myeloma cells used? (b) Do all cells growing in the selective medium produce antibodies to antigen X? (c) Why do only hybrid cells grow in the selective medium?
You wish to isolate a large amount of Fab fragments in order to examine their binding to protein X by X-ray crystallography. At first, you inject a large rabbit with protein X to obtain antibody. On further reflection, you decide to inject the antigen into a mouse in order to produce monoclonal
Why are the hypervariable sequences of immunoglobulins located in loops?
How do tissues with high metabolic activity facilitate oxygen delivery?
How would a lower p50 affect hemoglobin's oxygen acquisition in the lungs and oxygen delivery to the peripheral tissues?
Describe, on the molecular level, the role of myoglobin in O2 transport in rapidly respiring muscle tissue.
Explain why individuals with severe carbon monoxide poisoning are often given transfusions instead of oxygen-rich gas.
Match each of the structural elements of myoglobin or hemoglobin with its function below. A. His F8 B. His E7 C. E and F helices D. O2-Fe(II) E. Val E11 F. α1-β1 interface/α2-β2 interface G. oxymyoglobin/deoxymyoglobin H. oxyhemoglobin/deoxyhemoglobin I. α1-β2 interface/α2-β1
Estimate K from the following data describing ligand binding to a protein.
In humans, the urge to breathe results from high concentrations of CO2 in the blood; there are no direct physiological sensors of blood pO2. Skindivers often hyperventilate (breathe rapidly and deeply for several minutes) just before making a dive in the belief that this will increase the O2
The crocodile, which can remain under water without breathing for up to 1 h, drowns its air-breathing prey and then dines at its leisure. An adaptation that aids the crocodile in doing so is that it can utilize virtually 100% of the O2 in its blood whereas humans, for example, can extract only ~65%
Is the p50 higher or lower than normal in (a) Hemoglobin Yakima and (b) Hemoglobin Kansas? Explain.
In hemoglobin Rainier, Tyr 145β is replaced by Cys, which forms a disulfide bond with another Cys residue in the same subunit. This prevents the formation of ion pairs that normally stabilize the T state. How does hemoglobin Rainier differ from normal hemoglobin with respect to (a) Oxygen
In the variant hemoglobin C, glutamate at position 6 of the β chain has been replaced with lysine. (a) Would you expect this mutant hemoglobin to polymerize as hemoglobin S does? (b) Red blood cells containing hemoglobin C have a shorter lifespan than red blood cells containing normal hemoglobin.
In striated muscle, cells undergo mitosis (nuclear division) without cytokinesis (cellular division), giving rise to large multinucleate cells. Explain why muscle cells would be less effective if cytokinesis occurred with every round of mitosis.
A myosin head can undergo five ATP hydrolysis cycles per second, each of which moves an actin monomer by ~100 Å. How is it possible for an entire sarcomere to shorten by 1000 Å in this same period?
Which set of binding data is likely to represent cooperative ligand binding to an oligomeric protein?
Explain why a microfilament is polar whereas a filament of keratin is not.
Cells contain an assortment of proteins that promote microfilament disassembly during cell shape changes. How can such proteins distinguish newly synthesized microfilaments from older microfilaments?
Antibodies raised against a macromolecular antigen usually produce an antigen-antibody precipitate when mixed with that antigen. Explain why no precipitate forms when (a) Fab fragments from those antibodies are mixed with the antigen; (b) Antibodies raised against a small antigen are mixed with
Some bacteria produce proteases that can cleave the hinge region of IgA molecules without affecting antigen binding. Explain why these proteases would give the bacteria a better chance of starting an infection.
In active muscles, the pO2 may be 10 torr at the cell surface and 1 torr at the mitochondria (the organelles where oxidative metabolism occurs). Use Eq. 7-6 to show how myoglobin (p50 = 2.8 torr) facilitates the diffusion of O2 through these cells.
Individuals with systemic lupus erythematosus (SLE) produce antibodies to DNA and phospholipids. (a) Explain why normal individuals do not make antibodies to these substances. (b) During a normal response to a viral or bacterial infection, the immune system produces large amounts of
If myoglobin had the same p50 value as hemoglobin, how well would it facilitate O2 diffusion under the conditions described in Problem 3? In Problem 3 In active muscles, the pO2 may be 10 torr at the cell surface and 1 torr at the mitochondria (the organelles where oxidative metabolism occurs). Use
Use Eq. 7-8 to estimate the fractional saturation of hemoglobin when pO2 is (a) 20 torr, (b) 40 torr, and (c) 60 torr.
Calculate the p50 value for hemoglobin if YO2 = 0.82 when pO2 25 torr.
Drinking a few drops of a commercial preparation called "vitamin O," which consists of oxygen and sodium chloride dissolved in water, is claimed to increase the concentration of oxygen in the body. (a) Use your knowledge of oxygen transport to evaluate this claim. (b) Would vitamin O be more or
Explain why long-distance runners prefer to train at high altitude even when the race is to be held at sea level. Why must the runners spend more than a day or two at the higher elevation?
Some primitive animals have a hemoglobin that consists of two identical subunits. Sketch an oxygen-binding curve for this protein.
Indicate which of the following is an aldose, a ketose, a pentose, a hexose, a uronic acid, an alditol, a deoxy sugar, or a reducing sugar.
Glycogen and starch are extensively branched high-molecular-weight polymers. Suggest three reasons why such a structure is advantageous for a fuel-storage molecule.
How could lectins be used to purify polysaccharides and glycoproteins?
Figure 8-19 presents structures of typical N-linked oligosaccharides. (a) Which sugars make up the core oligosaccharide? (b) What other sugars are typically found at the termini of branched oligosaccharides?
The dissolution of blood clots involves hydrolysis of fibrin by the protease plasmin. Plasmin is activated by cleavage of inactive plasminogen by another protease called tissue plasminogen activator (tPA). tPA, in turn, must also be activated by proteolysis at a single site. Once plasmin is
A major protein of saliva contains several hundred identical covalently attached disaccharides containing N-acetylneuraminic acid in α(2→6) linkage to Nacetylgalactosamine that is linked to a Ser residue. Solutions of the intact protein are extremely viscous. However, when the protein is treated
Explain why a type AB individual can receive a transfusion of type A or type B blood, but a type A or type B individual cannot receive a transfusion of type AB blood.
Draw the following monosaccharides as Haworth projections: (a) α anomer of D-ribose (b) β anomer of D-glucose (c) β anomer of D-fructose (d) methyl-β-D-galactose. Which of these compounds contains a glycosidic bond?
Although β-D-glucopyranose is the predominant form of glucose in solution, crystalline glucose consists almost exclusively of α-D-glucopyranose. What accounts for this difference?
Draw the most stable chair conformation of α-D-galactose.
Match each term at the top with its definition below. A. Alditol B. Epimer C. Glycan D. Anomer E. Glycoside ____ Differs in configuration at the anomeric carbon ____ Polyhydroxy alcohol ____ Product of condensation of anomeric carbon with an alcohol ____ Differs in configuration at one carbon
Which of the following di- and trisaccharides contains fructose, contains an α anomeric bond, and/or is a reducing sugar?(a) Sucrose(b) Cellbiose (c) aLactose (d) Melibiose
An unknown trisaccharide was treated with methanol in HCl (to methylate its free OH groups) then subjected to acid hydrolysis (to break glycosidic bonds). The products were 2, 3, 4, 6-tetra-O-methylgalactose, 2, 3, 4-tri-O-methylglucose, and 2, 3, 6-tri-O methylglucose. Treatment of the intact
How do the chemical differences between starch and cellulose result in their very different polymeric structures?
(a) Deduce the structure of the disaccharide trehalose from the following information: Complete hydrolysis yields only D-glucose; it is hydrolyzed by α-glucosidase but not β-glucosidase; and it does not reduce Cu2+ to Cu+. (b) When exposed to dehydrating conditions, many plants and invertebrates
The artificial sweetener sucralose is a derivative of sucrose with the formal name 1,6-dichloro-1,6-dideoxy-β-D-fructofuranosyl- 4-chloro-4-deoxy-α-D-galactopyranoside. Draw its structure.
Draw the structure of the mannose trisaccharide that is part of the core N-linked oligosaccharide.
Cellulose is treated with methanol, which methylates free anomeric carbons. (a) How many methyl groups would be incorporated per cellulose chain? (b) Cellulose is treated with dimethyl sulfate, which adds a methyl group to all free hydroxyl groups. The cellulose is then hydrolyzed to release all
Glycogen is treated with dimethyl sulfate, which adds a methyl group to every free OH group. Next, the molecule is hydrolyzed to break all the glycosidic bonds between glucose residues. The reaction products are then chemically analyzed. (a) How many different types of methylated glucose molecules
"Nutraceuticals" are products that are believed to have some beneficial effect but are not strictly defined as either food or drug. Why might an individual suffering from osteoarthritis be tempted to consume the nutraceutical glucosamine?
Following their synthesis, many proteoglycans are stored in a highly condensed state in intracellular compartments. These compartments also contain many Ca2+ ions, which are rapidly pumped out as the proteoglycans are released extracellularly. Explain the function of the Ca2+ ions.
Draw the structure of the O-type oligosaccharide (the H antigen, described in Table 8-1).
During gel electrophoresis, glycoproteins migrate as relatively diffuse bands, whereas nonglycosylated proteins typically migrate as narrow, well-defined bands. Explain the difference in electrophoretic behavior.
Draw the furanose and pyranose forms of D-ribose.
Draw a Fischer projection of L-fucose. L-Fucose is the 6-deoxy form of which L-hexose?
Draw structures for the following fatty acids: (a) 18:0 octadecanoic acid (b) 20:4 5,8,11,14-eicosatetraenoic acid (c) 22:6 4,7,10,13,16,19-docosahexaenoic acid (d) 13-(2-cyclopentenyl)-tridecanoic acid (a cyclic fatty acid)
Why are eicosanoids called local mediators rather than hormones?
Summarize the functions of Vitamins A, D, E and K.
Explain why single-tailed amphiphiles tend to form micelles whereas two-tailed amphiphiles tend to form bilayers.
Why is a polar solute unlikely to penetrate a lipid bilayer?
Describe the structural changes that occur when a pure phospholipid bilayer is warmed and passes through its transition temperature. Explain what would happen if the bilayer contained a significant amount of cholesterol.
Summarize the physical properties of a typical integral protein, including the forces involved in its interaction with the membrane, its orientation, and its movement within the membrane.
List the principal lipids that are found in lipid rafts. Would a phospholipid with a high content of docosahexaenoic acid be a raft component?
How do the following alterations in the structures of fatty acids affect their physical properties? (a) Increasing the chain lengths of saturated fatty acids (b) Increasing the number of double bonds in unsaturated fatty acids (c) Changing a cis double bond in a fatty acid to a trans double bond
Mutated forms of the protein p21c-ras are associated with the development of a substantial proportion of tumors. However, a second mutation that changes the Cys residue in the Cterminal Cys-X-X-Y sequence of p21c-ras to some other residue inhibits its cancer-causing potential. What does this
In verifying the fluid mosaic model of biological membranes, Michael Edidin observed that fusion of mouse and human cell membranes was temperature dependent, such that fusion did not occur below 15°C but proceeded readily at 37°C. Explain this difference in terms of membrane properties.
Explain why an erythrocyte membrane that synthesizes too little spectrin is a sphere rather than a biconcave disk.
How did Kennedy and Rothman demonstrate that newly synthesized bacterial membrane phospholipids rapidly cross from the cytoplasmic side to the external side of the membrane
Explain why the flip-flop rate of phospholipids in biological membranes is far greater than in artificial lipid membranes.
In the secretory pathway, match each of the following terms with its description below. ____ free ribosome ____ signal peptide ____ signal recognition particle (SRP) ____ core glycosylation ____ membrane anchor ____ translocon ____ signal peptidase ____ membrane-bound ribosomes ____ SRP receptor A.
A membrane glycoprotein-synthesizing system was devised that contained endoplasmic reticulum membranes and all the necessary ingredients for the in vitro synthesis of a protein. The complete synthesis of the protein molecule required 40 minutes. When the detergent Triton X-100 was added within a
Draw and name a typical triacylglycerol.
Draw the structures of the following lipids: (a) 1-palmitoyl-2-oleoyl-3-glycerophosphatidylethanolamine (b) 1-stearoyl-2-arachidonoyl-3-glycerophosphatidylinositol
What distinguishes a plasmalogen from other glycerophospholipids?
What chemical moieties do sphingomyelin and gangliosides have in common and which are unique to each?
The compound shown below has been advertised as a dietary supplement that purportedly prevents obesity, heart disease, and the ill effects of aging. Based on its structure, what physiological function is it most likely to actually perform?
(a) How many turns of an α helix are required to span a lipid bilayer (~30 Å across)? (b) What is the minimum number of residues required? (c) Why do most transmembrane helices contain more than the minimum number of residues?
Predict the effect of a mutation in signal peptidase that narrows its specificity so that it cleaves only between two Leu residues.
Explain why a drug that interferes with the disassembly of a SNARE complex would block neurotransmission.
Draw the structure of a glycerophospholipid that has a saturated C16 fatty acyl group at position 1, a monounsaturated C18 fatty acyl group at position 2, and an ethanolamine head group.
How many different types of triacylglycerols could incorporate the fatty acids shown in Fig. 9-1?
What products are obtained when 1-palmitoyl-2-oleoyl-3- phosphatidylserine is hydrolyzed by (a) Phospholipase A1; (b) Phospholipase A2; (c) Phospholipase C; (d) Phospholipase D?
Sphingosine-1-phosphate can serve as a cell signaling molecule. (a) Draw the structure of this compound. (b) What chemical reactions must occur in converting a sphingomyelin molecule to sphingosine-1-phosphate?
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