End of Chapter Questions Flashcards
1
Q
Primary messenger def
A
Message received by the cell
2
Q
Secondary messenger def
A
Intracellular chemical that relays message from ligand receptor complex
3
Q
G-coupled receptor protein is composed of what?
A
Composed of seven transmembrane helices
3
Q
What is Heterotrimeric G-protein activated by?
A
Activated by 7TM receptor
4
Q
What does Gas activate?
A
Activates phospholipase C
5
Q
What is Protein kinase A stimulated by?
A
Stimulated by cAMP
6
Q
What does cAMP phosphodiesterase do?
A
inactivates protein kinase A
7
Q
GTPase activity results in
A
Results in the reassociation of Ga and Gby.
7
Q
Cholera is due to?
A
Due to persistant stimulation of Gas
8
Q
What does Pertussis result from?
A
Results from Gai inhibition
9
Q
What does Phospholipase C generate?
A
Generates two second messengers
10
Q
What does Gaq activate?
A
Activates Phospholipase C
11
Q
What does inositol triphosphate activate?
A
activates a Ca2+ channel
12
Q
What is protein kinase C activated by?
A
activated by diacylglycerol
13
Q
WHat are the three major classes of membrane receptors?
A
1) G-protein coupled, seven-transmembrane-helix receptors
2) receptors thatdimerize on ligand binding and recruit tyrosine kinases
3) receptors that dimerize on ligand bonding that are tyrosine kinases (receptor tyrosine kinases)
14
Q
Explain how a small number of hormones binding to the extracellular surface of a cell can have a large biochemical effect inside the cell.
A
The initial signal- the bondong of the hormone by a receptor- is amplified by enzymes and channels.
15
Q
What are some of the structural features common to all membrane-bound receptors?
A
the receptor must have a site on the extracellular side of the membrane to which the signal molecule can bind and must have an intracellular domain, Binding of the signal to the receptor must induce structural changes on the intracellular domain so that the signal can be transmitted.
16
Q
Why is the GTPase activity of G proteins crucial to the proper functioning of a cell?
A
The GTPase activity terminates the signal. Without such activity, after a pathway has been activated and is unresponsive to changes in the initial signal.
17
Q
Hormones affect the biochemistry of a distinct set of tissues. What accounts fir the tissue specificity of hormone action?
A
The presence of the appropriate receptor.
18
Q
Growth hormone binding causes what?
A
Causes receptor dimerization
19
Q
Growth hormone receptor
A
Activates JAK
20
Q
Receptor tyrosine kinase
A
Dimerization results in cross-phosphorylation
21
Q
Grb-2 bonds what?
A
Bonds receptor tyrosine kinase and Sos
22
Q
Sos
A
Activates Ras
23
Ras
Small G-protein
24
IRS
Adaptor protein in insulin signaling pathway
25
Phosphoinositide kinase binds what
Binds IRS and forms IP3
26
PIP3-activated kinase
Activates Akt
27
Akt promotes what?
Promotes movement of glucose transporters to the cell membrane
28
An experiment was done on the nature of receptor tyrosine kinase signaling where a gene was synthesized that encoded a chimeric receptor. The striking part was that the binding of insulin induced tyrosine kinase activity, as evident by rapid autophosphorylation. What does this result tell you about the signaling mechanisms of the EGF and insulin receptors?
The insulin receptor and the EGF receptor employ a common mechanism of signal transmission across the plasma membrane.
29
What is the difference between heterotrimeric G proteins and small G proteins?
Heterotrimeric G proteins are composed of alpha beta subunits. The alpha subunit contains the GTP-binding site. Upon activation by the signal receptor event, the GDP is exchanged for GTP, and the by subunits dissociate from the alpha subunit bound to the GTP, which then activates other pathway components such as adenylate cyclase. Small G proteins such as Ras are single-subunit proteins. They are activated by proteins such as Sos in the EGF signal pathway. The activation causes the exchange of GDP for GTP to activate Ras, which, in turn, activates specific kinases.
29
A mutated form of the alpha subunit of the heterotrimeric G protein has been indentified: this form readily exchanges GDP for GTP even in the absence of an activated receptor, What would be the effect on a signaling pathway containing the mutated alpha subunit?
The mutated alpha subunit would always be in the GTP form and, hence, in the active form, which would stimulate its signaling pathway
30
34
What is meant by intermediary metabolism?
The highly integrated biochemical reactions that take place inside the cell.
35
Differentiate between anabolism and catabolism
Anabolism is the set of biochemical reactions that use energy to build new molecules and, ultimately, new cells. Catabolism is the set of biochemical reactions that extract energy from fuel sources or break down bio molecules.
36
What is the cellular energy currency?
ATP
37
Anabolic electron carrier
NADP+
38
Phototroph
Converts light energy into chemical energy
39
Catabolic electron carrier
NAD+
40
Oxidation-reduction reaction
Transfers electrons
41
Activated carrier of two carbon fragments
Coenzyme A
42
Vitamin
Precursor to coenzymes
43
Anabolism
Requires energy
44
Catabolism
Yields energy
45
Amphibolic reaction
Used in anabolism and catabolism
46
What factors account for the high phosphoryl-transfer potential of nucleoside triphosphates?
Charge repulsion, resonance stability, increase in entropy, and stabilization by hydration.
47
Why does it make good sense to have a single nucleotide, ATP, function as the cellular energy currency?
Having only one nucleotide function as the energy currency of the cell enables the cell to monitor its energy status.
48
Metabolic pathways often contain reactions with positive standard free energy values, yet the reactions still take place, how?
The free energy changes of the individual steps in a pathway are summed to determine the overall free energy change of the entire pathway. Consequently, a reaction with a positive free energy value can be powered to take place if coupled to a sufficiently exergonic reaction.
49
What is the structural feature common to ATP,FAD,NAD+ and CoA?
An ADP unit
50
Glycolysis is a series of 10 linked reactions that convert one molecule of glusoce into two molecules of pyruvate with the concomitant synthesis of two molecules of ATP. The standard free energy for this reaction is -35.6 kj/mol, where as the free energy under intracellular conditions is -90 kj/ mol. Explain;the difference
Recall that free energy change= standard G +RT ln(prod/react). Altering the ratio of products to reactants will cause G to vary. In glycolysis, the concentrations of the components of the pathway result in a value of G greater than the standard G.
51
What are reasons that glucose is fuel used by all organisms?
Glucose is formed under prebiotic conditions. It is the most stable hexose sugar and has a low tendency relative to other monosaccharides to nonenzymatically react with proteins
52
Hexokinase
Phosphorylates glucose
53
Phosphoglucose isomerase
Converts glucose 6-phosphate into fructose 6-phosphate
54
Phosphofructokinase
Forms fructose 1,6-biphosphate
55
Aldolase
Cleaves fructose 1,6-biphosphate
56
Triose phosphate isomerase
Catalyzes the inter conversion of three carbon isomers
57
Glyceraldehyde 3-phosphate dehydrogenase
Generates the first high-phosphoryl-transfer-potential compound that is not ATP
58
Phosphoglycerate kinase
Generates the first molecule of ATP
59
Phosphoglycerate mutase
Converts 3-phosphoglycerate into 2-Phosphoglycerate
60
Enolase
Generates the second high-transfer potential compound that is not ATP
61
Pyruvate kinase
Generates the second molecule of ATP
62
Lactic acid fermentation and alcoholic fermentation are oxidation-reduction reactions. Identify the ultimate electron donor and electron acceptor
In both cases, the electron donor is glyceraldehyde 3-phosphate. In lactic acid fermentation, the electron acceptor is pyruvate, converting it into lactate. In alcoholic fermentation, acetaldehyde is the electron acceptor, forming ethanol.
63
How much ATP is generated from glucose 6-phosphate?
3 ATP
64
How much ATP is generated from dihydroxyacetone phosphate?
2 ATP
65
How much ATP is generated from glyceraldehyde 3-phosphate?
2 ATP
66
How much ATP is generated from fructose?
2ATP
67
How much ATP is generated from sucrose?
4 ATP
68
Why is it advantageous for the liver to have both hexokinase and glucokinase to phosphorylate glucose?
Glucokinase allows the liver to remove glucose from the blood when hexokinase is saturated, ensuring that glucose is captured for later use.
69
In the liver and the pancreas, hexokinase and glucokinase phosphorylate glucose. Glucokinase is active on,y when the blood concentration of glucose is high. How might glucokinase differ kinetically from hexokinase so as to function only at high glucose levels?
Glucokinase has a higher Km value, which allows this enzyme to become more active at high glucose concentrations- conditions that saturate hexokinase.
70
Why is the isomerization of glucose 6-phosphate to fructose 6-phosphate is an important step in glycolysis? How is the conversion of the fructose isomer back into the glucose isomer prevented?
Glucose cannot be cleaved into two three-carbon fragments, whereas fructose can, and three carbon molecules are metabolized in the second stage of glycolysis. The conversion of fructose 6-phosphate into fructose 1,6-biohosphate prevents the glucose isomer from being reformed.
71
The interconversion of DHAP and GAP greatly favours the formation of DHAP at equilibrium. Yet the conversion of DHAP by triose phosphate isomerase proceeds readily. Why?
The GAP formed is immediately removed by subsequent reactions, resulting in the conversion of DHAP into GAP by the enzyme.
72
Although both hexokinase and phosphofructokinase catalyze irreversible steps in glycolysis and the hexokinase-catalyzed step is first, phosphofructokinase is nonetheless the pacemaker of glycolysis. What does this information tell you about the fate of the glucose 6-phosphate formed by hexokinase?
Glucose 6-phosphate must have other fates. Indeed, it can be converted into glycogen or be processed to yield reducing power for biosynthesis.
73
Why can’t the reactions of the glycolytic pathway simply be run in reverse to synthesize glucose?
The free energy for the reverse of glycolysis is +90 kj/mol, far too endergonic to take place.
74
What are the principle fates of pyruvate generated in glycolysis?
Pyruvate can be metabolized to ethanol in alcoholic fermentation, to lactate in lactic acid fermentation, or it can be completely oxidized to CO2 and H2O in cellular respiration.
75
What reactions of glycolysis are irreversible under intracellular conditions?
The conversion of glucose into glucose 6-phosphate by hexokinase,
the conversion of fructose 6-phosphate into fructose 1,6-biphosphate by phosphofructokinase,
the formation of pyruvate formation from phosphoenolpyruvate by pyruvate kinase
76
What is the equilibrium ratio of phosphoenolpyruvate to pyruvate under standard conditions when ATP/ADP= 10
3.06x10^-5
77
Phosphofructokinase converts fructose 6-phosphate to fructose 1,6- biphosphate, the committed step on the pathway that synthesizes ATP. However, some fructose 6-phosphate is converted into fructose 2,6-biphsophate. Explain why depleting the substrate of phosphofructokinase to form fructose 2,6-biphosphate is not a wasteful use of substrate.
Substrates are usually present in much higher concentration than their enzymes. Consequently, converting a small amount of substrate into a potent activator of PFK will Lea to a rapid increase in the rate of ATP synthesis.
78
Glucose 6-phosphate inhibits what?
Inhibits hexokinase
79
Low ATP/ADP ratio does what
Stimulates phosphofructokinase
80
Citrate inhibits what
Inhibits phosphofructokinase in the liver
81
Low pH inhibits what?
Inhibits phosphofructokinase in muscles
82
Fructose 1,6-biohosphate stimulates what
Stimulates pyruvate kinase
83
Fructose 2,6-biphosphate stimulates what
Stimulates phosphofructokinase in the liver
84
Insulin cause what in cell membranes
Causes the insertion of GLUT4 into cell membranes
85
What has a high Km for glucose
Glucokinase
86
Transporter specific to liver and pancreas
GLUT4
87
High ATP/ADP ratio inhibits what
Inhibits phosphofructokinase
88
Fructose 2,6-biphosphate is a potent stimulator of phosphofructokinase. Explain how fructose 2,6-biphsophate might function in the concerted model for Allosteric enzymes.
Fructose 2,6-biphosphate stabilizes the R state of the enzyme
89
What reaction serves to link glycolysis and the citric acid cycle, and what is the enzyme that catalyzes the reaction?
The pyruvate dehydrogenase complex catalyzes the following reaction, which links glycolysis and citric acid:
Pyruvate + CoA + NAD+ -> acetyl CoA + NADH + H+ + CO2
90
What are the five enzymes that constitute the pyruvate dehydrogenase complex and what reactions do they catalyze?
Pyruvate dehydrogenase- catalyzes the decarboxylation of pyruvate and the formation of acetyllipoamide.
Dihydrolipoyl transacetylase- catalyzes the formation of acetyl CoA.
Dihydrolipoyl dehydrogenase- catalyzes the reduction of the oxidized lipoid acid.
PDH kinase- associated with the complex phosphorylates and inactivates the complex.
PDH phosphatase- dephosphorylates and activates the complex.
91
Acetyl CoA is released after the fourth step of the pyruvate dehydrogenase complex reaction cycle. What is the purpose of the remaining steps?
The remaining steps regenerate oxidized lipoamide, which is required to begin the next reaction cycle. Moreover, this regeneration results in the production of high energy electrons in the form of NADH.
92
The conversion of pyruvate into acetyl CoA consists of three steps. What are these steps?
Decarboxylation, oxidation, and transfer of the resultant acetyl group to CoA
93
The conversion of pyruvate into acetyl CoA commits the carbon atoms to either of the two principal fates. What are these fates?
Oxidation to CO2 by the citric acid cycle or incorporation into lipids.
94
What coenzymes are required by the pyruvate dehydrogenase complex and what are their roles?
Thiamine pyrophosphate plays a role in the decarboxylation of pyruvate.
Lipoic acid transfers the acetyl group
Coenzyme A accepts the acetyl group from lipoic acid to form acetyl CoA.
FAD accepts the electrons and hydrogen ions when oxidized lipoic acid is reduced.
NAD+ accepts electrons and a proton from FADH2.
95
Distinguish between catalytic coenzymes and stoichiometric coenzymes in the pyruvate dehydrogenase complex
Catalytic coenzymes (TPP, lipoic acid, FAD) are modified but regenerated in each reaction cycle. Thus, they can play a catalytic role in the processing of many molecules of pyruvate. Stoichiometric coenzymes (coenzyme A and NAD+) are used only in one reaction cycle because they are the components of products if the reaction.
96
When lipoamide is reoxidized, what is the intermediate electron acceptor and what is the final electron receptor of the reaction? Why is the observed electron transfer unusual?
The electrons are transferred from reduced lipoamide to FAD initially and then to NAD+. This transfer is unusual because the electrons are passed to NAD+ from FADH2. The transfer is usually in the other direction.
97
What is Acetyl CoA
The fuel for the citric acid cycle
98
Citric acid cycle
Is the central metabolic hub.
99
Pyruvate dehydrogenase complex catalyzes what?
Catalyzes the link between glycolysis and the citric acid cycle
100
Thiamine pyrophosphate
Coenzyme required by pyruvate dehydrogenase
101
Lipoic acid
Coenzyme required by transacetylase
102
Pyruvate dehydrogenase catalyzes what?
Catalyzes the oxidative decarboxylation of pyruvate
103
What is Acetyl-lipoamide?
The final product of pyruvate dehydrogenase
104
Dihydrolipoyl transacetylase
Catalyzes the formation of acetyl CoA.
105
Dihydrolipoyl dehydrogenase does what?
Regenerates active transacetylase
106
What is Beriberi
Due to a deficiency of thiamine
107
Compare the regulation of the pyruvate dehydrogenase complex in muscle and in liver
In muscle, the acetyl CoA generated by the complex is used for energy generation. Consequently, signals that indicate an energy-rich state inhibit the complex, whereas the reverse conditions stimulate the enzyme. Calcium as the signal for muscle contraction also stimulates the enzyme. In liver, acetyl CoA derived from pyruvate is used for biosynthetic purposes such as fatty acid synthesis. Insulin, the hormone denoting the fed state, stimulates the complex.
108
The complete oxidation of one molecule of acetyl coa by the cirtic acid cycle results in?
The generation of two molecules of CO2
109
The pyruvate dehydrogenase complex is mechanically and structurally similar to?
Alpha-ketoglutaratedehydrogenase
110
What is the net equation of the citric acid cycle?
Acetyl CoA + 3 NAD+ + FAD + ADP + P -> 2 CO2 + 3 NADH + 3H + FADH2 + ATP + CoA
111
The citric acid cycle is part of aerobic respiration, but no O2 is required for the cycle. Explain
The citric acid cycle depends on the su;ply of FAD and NAD+, which are generated by the reaction of FADH2 and NADH with oxygen. If there is no oxygen to accept the electrons, the citric acid cycle wont occur.
111
what are the two stages of the citric acid cycle?
First stage, two carbon atoms are introduced into the cycle by reacting with oxaloacetate to form citrate. Two carbon atoms are then oxidized to CO2
Second stage, the resulting four-carbon molecule is metabolized to regenerate oxaloacetate. High energy electrons are generated in both steps
112
Pyruvate dehydrogenase complex converts what to what?
Converts pyruvate into acetyl CoA
113
Citrate synthase condenses what?
condenses oxaloacetate and acetyl CoA
114
Aconitase catalyzes what?
Catalyzes the formation of isocitrate
115
isocitrate dehydrogenase catalyzes what?
catalyzes the formation of alpha-ketoglutarate
116
alpha-ketoglutaratedehydrogensase synthesizes what?
synthesizes succinyl CoA
117
Succinyl CoA synthetase generates what?
generates ATP
118
succinate dehydrogenase synthesizes what?
synthesizes fumarate
119
malate dehydrogenase catalyzes what?
catalyzes the formation of oxaloacetate
119
fumarase generates what?
generates malate
120
pyruvate carboxylase converts what to what?
converts pyruvate into oxaloacetate
121
The synthesis of citrate from acetyl CoA and oxaloacetate is a biosynthetic reaction. What is the energy source that drives the formation of citrate?
The reaction is powered by the hydrolysis of a thioester. Acetyl CoA provides the thioester that is converted into citryl CoA. When this thioester is hydrolyzed, citrate is formed in an irreversible reaction.
122
How is the wasteful hydrolysis of acetyl coa prevented by citrate synthase?
Acetyl coa does not bind citrate synthase until oxaloacetate is bound and ready for the synthesis of citrate.
123
Distinguish between a reducing agent and an oxidizing agent
an oxidizing agent, or oxidant, accepts electrons in a redox reaction
A reducing agent, or reductant, donates electrons in such reactions.
124
What is coenzyme Q
A lipid-soluble electron carrier
125
What does Q cycle do?
It funnels electrons from a two-electron carrier to a one-electron carrier
From ubiquinol (coenzyme Q) to cytochrome c.
126
Explain why coenzyme Q is an effective mobile electron carrier in the ETC
The 10 isoprene unites render coenzyme Q soluble in the hydrophobic environment of the inner membrane. The two oxygen atoms can reversibly bond two electrons and two protons as the molecule transitions between the quinone form and the quinol form
127
What is the proper order of the components of the electron transport chain
NADH-Q oxidoreductase, ubiquinone, Q-cytochrome c oxidoreductase, cytochrome c, cytochrome c oxidase
128
What does ATP synthase do
Converts the proton-motive force into ATP
129
what is the Proton-motive force composed of
Composed of a chemical gradient and a charge gradient
130
WHat generates the proton motive force?
The electron transport chain
131
What does the uncoupling protein result in?
Results in heat instead of ATP
132
WHat is the F1 subunit
catalytic subunit
133
What is the F0 subunit
Proton channel
134
What is the c ring?
A proton merry go round
135
WHat is the effect of azide on electron transport and ATP formation?
Azide blocks electron transport and proton pumping at complex 4
136
What is the effect of atractyloside on electron transport?
Atractyloside blocks electron transport and ATP synthesis by inhibiting the exchange of ATP and ADP across the inner membrane
137
What is the effect of rotenone on electron transport?
Rotenone blocks electron transport and proton pumping at complex 1
138
What is the effect of DNP on ATP synthesis?
DNP blocks ATP synthesis without inhibiting electron transport by dissipating the proton gradient
139
What is the effect of carbon monoxide on electron transport and ATP synthesis?
Carbon monoxide block electron transport and proton pumping at complex 4
140
WHat is the effect of Antimycin A on electron transport and ATP synthesis?
Antimycin A blocks electron transport and photon pumping at complex 4.
141
What is the mechanistic basis for the observation that the inhibitors of ATP synthase also lead to an inhibition of the electron transport chain?
If the proton gradient is not dissipated by the influx of protons into a mitochondrion with the generation of ATP, the outside of the mitochondrion eventually develops such a large positive charge that the electron transport chain can no longer pump protons against the gradient.
142
Before, it had been suggested that uncouplers would make a good diet drug. Why was this idea proposed and why was it rejected?
If oxidative phosphorylation were uncoupled, no ATP could be produced. In an attempt to generate ATP, much fuel would be consumed. Too much uncoupling could lead to tissue damage in the brain and heart. The energy that is normally transformed into ATP would be released as heat.
143
If actively respiring mitochondria are exposed to an inhibitor of ATP synthase, the electron transport chain ceases to operate why?
If the proton gradient cannot be dissipated by flow through ATP synthase, the proton gradient will eventually become so large that the energy released by the electron transport chain will not be great enough to pump protons against the larger gradient.
144
What is the actual role of protons in the synthesis of ATP by F0F1ATP synthase?
The proton gradient is necessary for ATP synthesis because proton flow through the enzyme causes conformational changes that convert a T subunit into an O subunit with the release of ATP. The role of the proton gradient is not to form ATP but to release it from the synthase.
145
Give an example of the use of the proton-motive force in ways other than for the synthesis of ATP
ATP export from the matrix. Phosphate import into the matrix
146
Describe the evidence supporting the chemiosmotic hypothesis
The ATP synthase would pump protons at the expense of ATP hydrolysis, thus maintaining the proton-motive force. The synthase would function as an ATPase. There is some evidence that damaged mitochondria use this tactic to maintain the proton-motive force.
147
What energetic barrier prevents glycolysis from simply running in the reverse to synthesize glucose? What is the energetic cost of overcoming this barrier?
The reverse of glycolysis is highly endergonic under cellular conditions. The expenditure of six NTP molecules in gluconeogenesis renders gluconeogenesis exergonic.
148
What is lactate converted into?
pyruvate
149
What is acetyl CoA required for in gluconeogenesis?
required for for pyruvate carboxylase activity
150
What does pyruvate carboxylase generate?
generates oxaloacetate
151
What does phosphoenolpyruvate carboxykinase generate?
Generates a high-phosphoryl-transfer-potential compound
152
What is glycerol readily converted into in gluconeogenesis?
converted into DHAP
153
What is fructose 1,6-biphosphatase in gluconeogenesis?
The gluconeogenic counterpart of PFK
154
Where is glucose 6-phosphate primarily found?
In the liver
155
What reactions of glycolysis are not reversible under cellular conditions? How are these reactions bypassed in gluconeogenesis?
The formation of pyruvate and ATP by pyruvate kinase is irreversible and is bypassed by two reactions in gluconeogenesis:
1- the formation of oxaloacetate from pyruvate and CO2 by pyruvate carboxylase
2- the formation of phosphoenolpyruvate from oxaloacetate and GTP by phosphoenolpyruvate carboxykinase.
The formation of fructose 1,6-biphosphate by PFK is bypassed by fructose 1,6-biphosphate, which catalyzes the conversion of fructose 1,6-biphosphate into fructose 6-phosphate.
The hexokinase-catalyzed formation of glucose 6-phosphate in glycolysis is bypassed by glucose 6-phosphatase, only in the liver.
156
Liver is primarily a gluconeogenic tissue, whereas muscle is primarily glycolytic. WHy does this division of labor make good physiological sense?
Muscle is likely to produce lactic acid during contraction. Lactic acid is a strong acid and must not accumulate in muscle or blood. Liver removes the lactic acid from the blood and converts it to glucose. The glucose can be released into the blood or stored as glycogen.
157
Why does the lack of glucose 6-phosphatase activity in the brain and muscle make sense?
Glucose is an important energy source for the brain and muscles and is essentially the only enenrgy source for the brain. Consenquently, these tissues should never release glucose. The release of glucose can be prevented by the absence of glucose 6-phosphatase.
158
Compare the roles of lactate dehydrogenase in gluconeogenesis and in lactic acid fermentation
In gluconeogenesis, lactate dehydrogenase synthesizes pyruvate from lactate. In lactic acid fermentation, the enzyme synthesizes lactate from pyruvate.
159
WHat are the two potential substrate cycles in the glycolytic and gluconeogenic pathways?
One would require the glycolytic enzyme PFK and the gluconeogenic enzyme fructose 1,6-biphosphatase
The other cycle would require pyruvate kinase from glycolysis and pyruvate carboxylase and phosphoenolpyruvate carboxykinase from gluconeogenesis.
160
Describe the reciprocal regulation of glycolysis and gluconeogenesis
The enzymes in two substrate cycles are control points. The glycolytic pathway is activated by F-2,6-BP, AMP, and F-1,6-BP, whereas ATP, alanine, citrate, and protons inhibit glycolysis. Gluconeogenesis is activated by citrate and acetyl CoA and inhibited by F-2,6-BP, AMP, and ADP.
160
What is the regulatory role for the substrate cycles in glycolysis and gluconeogenesis?
The substrate cycles regulate flux on one or the other pathway by amplifying metabolic signals.
161
What conditions increase the activity of glycolysis?
Increase in AMP, Increase in F-2,6-BP, Increase in insulin, Fed
162
What is the minimum number of contiguous bases required to encode 20 amino acids?
Three contiguous bases. Because there are four bases, a code is based on a two-base codon could encode only 16 amino acids. A three-base codon would allow 64 different combinations, more than enough to account for the 20 amino acids.
163
WHy has the code remained nearly invariant through billions of years of evolution, from bacteria to human beings?
A mutation that altered the reading of mRNA would change the amino acid sequence of most, if not all, proteins synthesized by the particular organism. many of these changes would undoubtedly be deleterious, so there would be strong selection against a mutation with such persuasive consequences.
164
What is thw wobble
pairing freedom
165
What is aminoacyl-tRNA synthetase?
The code reader
166
What are the key characteristics of the genetic code?
Three nucleotides encode an amino acids; the code is nonoverlapping; the code has no punctuation,; the code is degenerate
167
What does it mean that the code is degenerate and why is it a good thing?
Degeneracy of the genetic code means that for most amino acids, there is more than one codon that calls for it. This is valuable because if not, there would be only 20 codons that call for amino acids and the rest would be chain terminating, and mutations would lead to inactive proteins.
168
Why is it crucial that protein synthesis have an error frequency of 10^-4?
Higher error rates would result in too many defective proteins. Lowers error rates would likely slow the rate of protein synthesis without a gain in accuracy.
169
Explain how it is possible that some tRNA molecules recognize more than one codon
The first two bases in a codon form Watson-Crick base pairs that are checked for fidelity by bases of the 16S rRNA. The third base is not inspected for accuracy, so some variation is tolerated.
170
What two reaction steps are required for the formation of an aminoacyl-tRNA?
First is the formation of aminoacyl adenylate, which then reacts with the tRNA to form the aminoacyl-tRNA. Both steps are catalyzed by aminoacyl-tRNA synthetase.
171
Why must tRNA molecules have both unique structural features and common structural features?
Unique features are required so that the aminoacyl-tRNA synthetases can distinguish among the tRNAs and attach the correct amino acid to the correct tRNA. Common features are required because all tRNAs must interact with the same protein-synthesizing machinery.
172
The energetic equivalent of two molecules of ATP is used to activate an amino acid, yet only one molecules of ATP is used. Explain.
ATP is cleaved to AMP and PPi. Consequently, a second ATP is required to convert AMP into ADP, the substrate for oxidative phosphorylation
173
RNA is readily hydrolyzed by alkali, whereas DNA is not Why?
The 2'-OH group in RNA acts as an intramolecular nucleophile. In the alkaline hydrolysis of RNA, the 2'-OH group forms a 2'-3'cyclic intermediate.
174
Why is protein synthesis also called translation?
The definition of translation is the actoin or process of turning from one language into another. Protein synthesis converts nucleic-acid-sequence information into amino-acid-sequence information.
175
What is meant by the term reading frame?
The reading frame is a set of contiguous, nonoverlapping, three-nucleotide codons that encode the amino acid sequence of the protein. The reading frame begins with a start codon and ends with a stop codon.
176
Ribosomes accelerate the hydrolysis of GTP bound to the complex of EF-Tu and aminoacyl-tRNA. WHat is the biological significance of this enhancement of GTPase activity by ribosomes?
GTP is not hydrolyzed until aminoacyl-tRNA is delivered to the A site of the ribosome. AN earlier hydrolysis of GTP would be wasteful because EF-Tu-GDP has little affinity for aminoacyl-tRNA.
176
tRNA molecules are quite large, the anticodon consists of only three nucleotides so what is the rest of the molecule used for?
tRNAs have roles in several recognition processes. A tRNA must be recognized by the appropriate aminoacyl-tRNA synthetase, and the tRNA must interact with the ribosome and the peptidyl transferase.
177
EF-Tu a G protein, plays a crutial role in the elongation process of translation. Suppose that a slowly hydrolyzable analog of GTP was added to an elongating system. WHat would be the effect on the rate of protein synthesis?
The rate would fall because the elongation step needs the GTP to be hydrolyzed before any further elongation can take place.
178
What is the a-ketoacid formed by the transamination of Alanine?
Pyruvate
179
What is the a-ketoacid formed by the transamination of Aspartate?
oxaloacetate
180
What is the a-ketoacid formed by the transamination of Glutamate?
a-ketoglutarate
181
What is the a-ketoacid formed by the transamination of leucine
b-ketoisocaproate
182
What is the a-ketoacid formed by the transamination of phenylalanine?
Phenyl pyruvate
183
What is the a-ketoacid formed by the transamination of tyrosine?
hydroxyphenylpyruvate
184
Glutamate dehydrogenase is considered unusual in that it does not discriminate between NADH and NADPH. Explain why this is unusual.
Most enzymes are specific to one or another. Enzymes in catabolic pathways use NADH/NAD+, whereas ezymes in anabolic pathways use only NADPH/NADP+.
185
How do aminotransferases and glutamate dehydrogenases cooperate in the metabolism of the amino group of amino acids.
Aminotransferases transfer the a-amino group to a-ketoglutarate to form glutamate, which is oxidatively deamined to form an ammonium ion.
186
What amino acids yield citric acid cycle components and glycolysis intermediates when deaminated?
Asparate- oxaloacetate
Glutamate- a-ketoglutarate
alanine-pyruvate
187
What amino acids can be deamined directly?
serine and threonine
188
What are the immediate biochemical sources for the two nitrogen atoms in urea?
Carbamoyl phosphate and aspartate.
189
How is the urea cycle linked to the citric acid cycle?
The synthesis of fumarate by the urea cycle is important because it links the two cycles. Fumarate is hydrated to malatae, then oxidized to oxaloacetate which has several possible fates:
1. transamination to asparatate,
2. conversion into glucose by gluconeogenesis,
3. condensation with acetyl CoA to form citrate
4. conversion into pyruvate
190
differenciate between ketogenic and glucogenic amino acids
The carbon skeleton of ketogenic amino acids can be converted into ketone bodies or fatty acids. (only leucine and lysine)
Glucogenic amino acids can be converted into glucose.
191
Define nitrigen fixation and what organisms are responsible for nitrogen fixation?
Nitrogen fixation is the conversion of atmospheric N2 to NH4+. Diazotrophic (nitrogen-fixing) microorganisms are responsible for this reaction
192
What is the role of ATP is nitrogen fixation?
The fixation of nitrogen is exergonic. The role of ATP is to reduce the activation energy of the barriers u=in the reaction pathway so as to render the reaction kinetically feasible.
193
What are the two components of the nitrogenase complex and what do they do?
Reductase and nitrogenase
The reductase provides the electrons with high reducing power and the nitrogenase uses the electrons to reduce N2 to NH4+.
194
Is nitrogen fixation a thermally unfavourable process?
No, it is thermodynamically favourable. ATP expenditure by the nitrogenase is required to make the reaction kinetically possible.
195
WHat cofactor is required by all aminotransferases?
pyridoxal phosphate (PLP)
196
WHat is the role of tetrahydrofolate in biochemical systems?
it is a carrier of a variety of one-carbon units
197
Differentiate between S-adenosylmethionine and tetrahydrofolate
Both carry one-carbon units. SAM is a more useful methyl donor than tetrahydrofolate because it has greater transfer potential. t
198
Differentiate between the de novo pathway and the salvage pathway for the synthesis of nuclotides
The de novo pathway, nucleotides are synthesized from simpler precursor compounds, like from scratch. The salvage pathway, the nucleotides are formed from premade bases that were recovered and attached to activated riboses.
199
Differentiate between a nucleoside and a nucleotide.
A nucleoside is a base and a ribose group whereas a nucleotide is a nucleoside plus one or more phosphates
200
What is excessive urate knwon as?
Gout
201
What is lack of adenosine deaminase?
Immunodeficiency
202
What does lack of HGPRT cause ?
Lesch-Nyhan Syndrome
203
WHat is carbamoyl phosphate synthetase used for?
tThe first step in pyrimidine synthesis.
204
What is inosinate used to make?
It is the precursor to both ATP and GTP.
205
Ribonucleotide reductase is used for what?
Deoxynucleotide synthesis
206
Lack of folic acid causes what?
Spina bifida
207
Glutamine phosphoribosyl transferase is used for what?
The committed step in purine synthesis
208
What is the precursor to CTP
UTP
209
What major biosynthetic reactions utilize PRPP?
PRPP is the activated intermediate in the synthesis of phosphoribosylamine in the de novo pathway of purine synthesis, in the synthesis of purine nucleotides from free bases by the salvage pathway, and in the synthesis of orotidylate in the formation of pyrimidines.
210
What is the reciprocal substrate relation in the synthesis of ATP and GTP?
AMP synthesizes GTP and GMP synthesizes ATP. This relation tends to balance the synthesis of ATP and GTP.
211
How many molecules of ATP are required to synthesize one molecule of CTP from scratch?
Total 7 ATP.
212
Human beings contain two different carbamoyl phosphate synthetase enzymes. One uses glutamine as a substrate whereas the other uses ammonia. What are the functions of these two enzymes?
CP 1 uses ammonia to synthesize carbamoyl phosphate for a reaction with ornithine, the first step of the urea cycle. CP2 uses glutamine to synthesize carbamoyl phosphate for use in the first step of pyrimidine biosynthesis.
213
WHat is a Watson-Crick base pair?
Hydrogen bonding between the base A and T and between G and C
214
What does base stacking do?
Stabilizes the double helix structure due to van der waals interactions
215
What is the most common form of DNA?
B-DNA
216
at is A-DNA
A form of DNA found under dehydrating conditions
217
Why does heat denature DNA in solution?
The thermal energy causes the strands to wiggle, disrupting the hydrogen bonds between base pairs and the stacking forces between bases so the strands separate.
218
Define template and primer as they relate to DNA synthesis
A template is the sequence of DNA or RNA that directs the synthesis of a complementary sequence. A primer is the initial segment if a polymer that is to be extended on which elongation depends.
219
Explain why DNA synthesis depends on RNA synthesis?
DNA polymerase cannot initiate primer synthesis. COnsequently, an RNA polymerase, called primase, synthesizes a short sequence of RNA that is used as a primer by the DNA polymerase
220
What are okazaki fragments
Short segments of DNA that are synthesized on the lagging strand of DNA. These fragments are joined by DNA ligase to form a continuous segment
221
Distinguish between the leading and lagging strand in DNA synthesis
The leading strand can be synthesized continuously in the 5'-3' direction whereas lagging strand is synthesized in short okazaki fragments.
222
What does telomerase do?
Prevents the disappearance of the lagging strand
223
How could you make DNA radioactive if you have a DNA endonuclease that cleaves the DNA internally to generate 3'-OH and 5'phosphoryl groups, intact DNA polymerase 1, and radioactive dNTPs?
Treat the DNA briefly with endonuclease to occasionally nick each stand. Add the polymerase with the radioactive dNTPs. At the broken bond, the polymerase will degrade the existing strand with its 5' - 3' exonuclease activity and replace it with a radioactive complementary copy by using its polymerase activity. This reaction scheme is referred to as nick translation because the nick is moved, or translated, along the DNA molecule without ever becoming sealed. radioactive
224
Define transcription
Transcription is DNA-directed RNA synthesis by RNA polymerase
225
What is the difference between the coding strand and the template strand?
The template strand has a sequence complementary to that of the RNA transcript. The coding strand has the same sequence as that of the RNA transcript except T in the place of U.
226
What are the three stages of RNA synthesis?
Initiation, elongation, termination
227
What components does RNA polymerase need to synthesize RNA?
Requires a DNA template, ribonucleotide phosphates (GTP, CTP, ATP, UTP) and Mg2+ or Mn2+
228
WHat is the function of the sigma subunit in transcription
The sigma subunit helps the RNA polymerase find the promoter sites. After the promoter site is located, the sigma subunit leaves the enzyme and can help another polymerase.
229
What does a repressor do?
It prevents the transcription of structural genes
230
Compare transcription with replication
Transcription uses DNA as a template, one strand is copied, RNA polymerase is the enzyme, ribonucleotides are the substrates and requires no primer.
Replication uses zDNA as the template as well, Both stranda are copies, the enzyme is DNA polymerase, the substrates are deoxyribonucleotides, and a primer is required.
231
WHat is a promoter?
A promoter is a DNA sequence that directs RNA polymerase to the proper initiation site for transcription
232
Distinguish between a closed promoter complex and an open promoter complex
In a closed promoter comples, the DNA is double helical and transcription is not possible. In the open promoter complex, the DNA is unwound, which is required for transcriptions.
233
WHy is RNA synthesis not as closely monitored for errors as DNA synthesis?
In RNA synthesis, an error affects only one molecule of mRNA of many synthesized from a gene. Also, the errors do not become a permanent part of the genomic information.
238
