Problem 1: Multiple Choice Madness For problems 1-15 choose the best answer. Write this letter (choice) in the box provided.

Transcription

1 Problem 1: Multiple Choice Madness For problems 1-15 choose the best answer. Write this letter (choice) in the box provided. 1) Proton pumps are extremely important in a number of biochemical processes. Which of the following statements accurately describes proteins in this family? A) P-type proton pumps function mainly to acidify intracellular vacuoles. B) Proton pumps all require ATP for phosphorylation and conformational change. C) With F-type proton pumps, H + s move toward the same compartment in which ATP is made. D) V-type and P-type proton pumps share a "head" and "stalk" general structure. E) None of the above is true. 2) In a living cell the Q for a particular reaction is 1 x 10 6, what can you conclude about this reaction under these conditions? A) The ΔG' of this reaction is negative. B) The ΔG of this reaction is negative. C) This reaction is spontaneous in the cell under these Copy conditions. D) This reaction is highly favorable in the cell under these conditions. E) None of the above can be concluded. F) More than one of the above can be concluded. 3) Different blood types, for example A, B, etc., arise because of differences in A) the carbohydrate groups found mainly on the phosphoglycerides of erythrocytes. B) glycoproteins that reside in the red blood cell membranes. C) the fatty acids linked to glycolipids in erythrocyte membranes. D) glycosylation of both membrane-bound and soluble biomolecules of the blood. E) the specific glycosylation of all antibodies within the bloodstream. F) More than one of the above is true 4) Absorption of nutrients by the intestinal epithelial cells is an essential process. Based on the absorption mechanism specifically modeled in class, the transporter used to move glucose from the epithelial cells to the blood stream A) utilizes an antiporter mechanism with K +. B) uses a uniporter. C) requires an active transporter. D) is electrogenic. E) requires a Na + /glucose symporter. F) More than one of the above is true. 5) Which of the following statements accurately describes the normal progression of events that takes place in any of the main GPCR hormonal cascades introduced in class? A) Protein Kinase A becomes activated and catalyzes the production of camp. B) Gq proteins bind to DAG, initiating the release of calcium from intracellular reservoirs. C) Phospholipase C catalyzes the production of PIP 3, a membrane-bound second messenger. D) Protein Kinase C is activated when camp binds to its regulatory subunits. E) None of the above is true. F) More than one of the above is true. 10

2 Problem 1 Continues 6) Which of the following statements regarding the non structural roles of lipids is false? A) Hormones that are not sex hormones are derived from sterols. B) Prostaglandins are derived from membrane bound fatty acids and play a role in inflammation. C) Bile acids are used to dissolve nonpolar dietary material so they contain very polar sites. D) Eicosanoids are signal molecules shipped through the bloodstream to their target cells. E) Leukotrienes are derived from ω-fats and play a role in lung function. 7) The Na/K pump plays an important role in virutally all cells, but which of the following statements accurately describes its primary function(s) and effects? A) Its electrogenic and passive transport activity establishes electrochemical gradients. B) It creates the "maximally depolarized" membrane potential observed in nerve signals. C) It creates the potassium gradient required for import of dietary glucose in intestinal epithelia. D) Its activity renders cells impervious to mobile ionophores like valinomycin. E) None of the above is true. F) More than one of the above is true. Copy 8) During the propagation of a nerve signal down an axon and across a synaptic cleft heading toward a muscle cell, A) calcium ions play an essential role in causing an action potential in the presynaptic axon. B) vesicles containing acetylcholine cross the synapse and fuse to the postsynaptic axon. C) neurotransmitter binding stimulates the active transport of cations in the postsynaptic axon. D) passive flow of potassium in the presynaptic axon leads to maximum depolarization. E) None of the above. 9) Which of the following statements about membrane proteins is false? A) Lateral movement of proteins through the bilayer is faster than tranverse movement. B) The membrane protein caveolin is generally embedded in a mono-layer of a membrane. C) Transmembrane proteins are arranged so that their amino terminus is cytosolic. D) Hydropathy plots may be used to predict whether a protein is embedded in a membrane. E) More than one of the above is false. F) None of the above is false. 10) Red bloods cells provide an important example of how transporters work together. In a red blood cell (RBC, erythrocyte) passing through deep tissue A) [bicarbonate] is lower in the plasma/rbc than it would be if the RBC is in the lungs. B) carbonic anhydrase is catalyzing production of C 2 more favorably than the reverse reaction. C) Band 3 is likely to be passively allowing Cl - into the RBC. D) carbonic anhydrase is catalyzing the carbamoylation of hemoglobin. E) carbon dioxide undergoes facilitated diffusion in order to enter the RBC. F) More than one of the above is true. 10

3 And some more... 11) Which of the following statements regarding trimeric G proteins is true? A) The β- and γ- subunits serve as GEFs, facilitating replacement of GTP with GDP. B) GAPs are proteins that replace bound GDP for GTP in the α-subunit. C) G protein α subunits may bind to target enzymes and repress activity. D) Conformational change in Gα is based on the loss of hydrogen bonding to the nucleoside. E) Cholera toxin directly binds to the α-subunit active site in place of a guanine nucleotide. 12) Glycogen synthesis and breakdown are coordinated in their regulation. Which of the following is a false statement regarding these processes and their regulation? A) The glycogenin Tyr is covalently bound to a glycogen polymer during synthesis alone. B) Synthesis and breakdown of glycogen both occur enzymatically at non-reducing ends only. C) Both synthesis and breakdown require enzymes that alter the branching of the polymer. D) A phosphorylated glucose is the product of phorphorylase and the substrate for synthase. E) Phosphorylation of synthase and phosphorylase results from the same hormonal cascade. F) More than one of the above is false. Copy 13) Vitamin A (retinol) is a biologicially significant compound because it A) is necessary for the formation of β-carotene in mammals. B) is directly and enzymatically converted to retinoic acid, a hormone that affects gene activity. C) is easily reduced to retinal, an important cofactor in visual transduction. D) contains unsaturation that becomes the basis for light-induced isomerization in retinal. E) More than one of the above is true. F) None of the above is true. 14) Proteins may be associated with biological membranes in a number of ways, including A) lipid links in which proteins are buried among fatty acid tails of the membrane. B) integrally, requiring lipase activity to release the protein from the membrane. C) peripherally, requiring detergents for their complete release from membranes. D) amphitrophically, with reversible association at membrane surfaces. E) All of the above are true. F) None of the above are true. 15) Individual proteins belonging to the class known as ABC-transporters (as discussed in Rees et al., 2009) have been observed to do all of the following except: A) move membrane lipids from one leaflet of the biological membrane to the other. B) move solutes from a compartment of low concentration to a higher concentration. C) transport lipophilic material in either direction, depending on the concentration gradient. D) cause resistance to therapeutic chemicals utilized to address cellular disorders. E) utilize an "alternating access" model based on conformational change. F) They do all of the above. 10

4 Page 4 A. The production of camp from ATP is an extremely important reaction for the propagation of some hormonal cascades. Provide the curved arrow mechanism for this reaction, draw the product(s) and provide the other missing information. (a) Curved arrow mechanism; show all electron movement efficiently camp P P P H NH 2 N N N N H (b) enzyme: + H B B Copy (b) enzyme: inorganic phosphate, P i B. Each of the following compounds plays some critical role in glycolysis and/or gluconeogenesis. For a-d, complete the reaction; for e-f, identify and describe the compound. Complete the single reaction involving the product shown (a) all substrate(s): (e) Identify: gluconeogenesis P (b) enzyme: P H Complete the single reaction involving the substrate shown (d) all product(s): glycolysis H H (f) Describe the role(s) of this compound P (c) enzyme: 14

5 Page 5 Consider the following table containing ΔG' values for the hydrolysis of various phosphorylated compounds. Phosphoenolpyruvate + H 2 Reaction Pyruvate + P i A. Consider the following reaction running at 25 C: ΔG' (kj/mol) ATP + H 2 ADP + P i Creatine phosphate + H 2 Creatine + P i Glucose-1-phosphate + H 2 Pyruvate + ATP Glucose + P i Phosphoenolpyruvate + ADP X (a) Calculate ΔG' (b) Calculate Keq'º Copy (c) If the ratio of ATP to ADP in the immediate surroundings is 10:1, what is the ratio of Pyruvate to PEP? (d) This reaction plays a critical role in the regulation of glycolysis and gluconeogenesis - what is this role and how is this reaction carried out (discuss the enzyme(s) responsible for the forward and reverse reaction? Discuss exactly how the ATP/ADP ratio impacts this reaction. B. Creatine phosphate is another high energy compound and its hydrolysis can drive other reactions. Consider the following reaction running at 25 C: Creatine phosphate + Glucose Creatine + Glucose-1-phosphate K eq = 7790 (a) Use this information to solve for the X in the table above (ΔG'º for glucose-1-phosphate hydrolysis): (b) If the Q calculated for this reaction is ~5 x 10 3 in the cell, is the reaction favorable? (c) Discuss the conditions and cell type that makes use of this reaction. 16

6 Page 6 A. The following images represent various roles that vesicles play in biochemical processes you have studied. Identify the images (each should have enough information to identify it uniquely), and briefly describe what the function performed by the vesicle shown. β-adrenergic receptor (e) Identify (a) Protein N+ (c) Protein (b) Role of the vesicle: (d) Role of the vesicle: (f) Role of the vesicle: Copy B. Membrane building blocks (a-d, below) also play significantly different roles based on their structures. Name using the C-skeleton and ω system Common name H 3N a Common name H H c P R(fatty acid C chain) b R(fatty acid C chain) Name using the C-skeleton and ω system NH R (fatty acid C chain) d C. T/F questions about the structures shown in parts A and B above. Vesicle fusion may involve special lipids called SNAREs. From part B above: Compound a will have a higher melting point than Compound d. Rafts contain unique proteins but are indistinguishable from surrounding areas in lipid composition. Gangliosides are derived from Compound c (in part B above). Phosphatidyl inositol is a glycolipid belonging to the phospholipid family. TAGs (triacylglycerols) do not belong to the membrane lipids family. 19

7 Page 7 A. The following questions address the transport events related to funny current and various other ion movements that occur in the contraction of cardiac muscle. (a) "Funny currents" occur at the -60 mv stage of the sinoatrial action potential, as shown (i f ). Assuming these currents are solely due to sodium concentration imbalance and the system is at equilibrium (you should assume ΔG=0), calculate the ratio of sodium concentration, C in /C out required in order to establish this membrane potential. Z" (b) The slow movement of Ca 2+ ions into the cell leads to a changing membrane potential until electrical repulsion prevents this movement. At this point, a three-fold concentration gradient still exists (C out /C in ); what must the membrane potential be (show signs!) in order to prevent further movement of calcium? Copy (c) T/F questions regarding this figure. B. Leading to point Z (section 0), the membrane is becoming hyperpolarized. Z marks the point where sodium ions rush back into the cell. The sections of this figure denoted as "4" represent a membrane at rest. As with most electrical signals, potassium movement is prominent during repolarization This figure represents one part of a sensory cascade that you know. (a) Using the concentrations and membrane potential initially, calculate the ΔG t for K + leaving this cell. Initially: V m = -33 mv [K + ] out = 0.5 mm [K + ] in = 6.5 mm stimulus (b) Based on the stimulus event shown (circle the best for each set) (i) this channel is: (ii) the cell is likely to: ligand-gated voltage-gated neither both hyperpolarize depolarize remain unchanged (c) What sensory cascade is involved here? 13

8 Page 8 A. The importing of vitamins may be facilitated by proteins of the ABC class. This is illustrated wtih the figure below (as in Rees et al. 2009). a and b are referring (a) Fill-in (b) Fill-in to the orientation of the protein complex -facing -facing in the figure (c) Protein (d) specific area of protein (e) bound nucleotides (e) bound nucleotides (f) specific area of protein B. This figure represents a regulatory point in several Copy metabolic processes. Identify and describe. (a) What type of cell is this? (b) Protein X (c) Describe the regulation of X: V m = -63 mv 1.8 mm favored 5.3 mm X (d) Enzymes (f) Enzyme (d) Enzyme 6-phosphogluconate (e) Product/effector Glucose 1- phosphate (f) Under the condition (favored) shown above, discuss the likely global hormonal state of the organism and this cell specifically. (g) Using the concentrations and membrane potential given in the figure, calculate the ΔG t for glucose entering this cell. 17

9 Page 9 A. The cascade involved in the visual response relies heavily on a cofactor/coenzyme that binds to the opsin through the formation of a protonated Schiff base. The Schiff formation may be shown in two mechanistic steps, using HB + and B in each step, with the net production of H 2. Please show this mechanism in its entirety. You may abbreviate the cofactor using an R for the bracketed portion. (a) step one (b) draw the intermediate and the curved arrow mechanism for step two (c) protonated Schiff product opsin N H H H R Copy + H 2 (d) Provide the name (as specifcally as possible) for this cofactor: B. Speaking of the visual cascade...identify and answer the questions. (a) A (before light) and B (after light) represent two states of rhodopsin, which is more likely to be holding the cofactor as it is shown above? (circle one) (c) protein (d) protein (e) reaction catalyzed (b) Name the cell and name the membrane A (c)(d) (d) (f) transporter (l) protein B (g) what causes binding? (k) protein (h) transporter (j) protein (i) protein 22

10 Page 10 Cascade roulette A. The figures below utilize a common effector. Label as directed and explain! (c) Protein (a) Proteins in this complex (g) This represents: (d) Protein (b) In the state indicated above, this complex is (circle one): (e) Protein (f) The end result: B. The figures below depict events that occur when Copy erythropoietin (EP) binds to its receptor. EP (a) Identify X: (b) Identify Z: T/F questions based on this scenario: Z X Z (c) (d) (e) (f) The EP receptor has inherent tyrosine kinase activity. Z is phosophorylated by this receptor. EP is a signal molecule involved in the development of red blood cells. The dimerized form of Z represents the inactive state of the complex. C. Complete the reactions! (a) substrate(s) and cofactor(s): (a) product(s): lactate dehydrogenase (a) substrate(s) and cofactor(s): under anaerobic conditions (b) enzyme: P H P 22