Lesson 2: Citric Acid Cycle (Krebs Cycle) & The Electron Transport Chain

High, Low

A ____ energy state to a ___ energy state is the basis of the electron transport chain

Oxidation/Reduction Reaction

A dehydrogenase enzymes indicates that which reaction is going to take place?

Chemiosmosis

A process for synthesizing ATP using the energy of an electrochemical gradient and the ATP synthase enzyme.

Aldol condensation

A reaction in which an aldehyde or ketone acts as both the electrophile and nucleophile, resulting in the formation of a carbon-carbon bond in a new molecule called an aldol.

Electron Transport Chain

A sequence of electron carrier molecules (membrane proteins) that shuttle electrons during the redox reactions that release energy used to make ATP.

Coenzyme Q (Ubiquinone)

A small non-protein electron carrier in the electron transport chain. It's a small hydrophobic molecule that's dissolved in the inner mitochondrial membrane. It shuttles electrons from complex 1&2 to complex 3

Complex 5

ATP synthase of the electron transport chain is sometimes also know as?

Dehydration & Hydration Reaction

Aconitase in step 2 of the citric acid cycle makes citrate undergo what 2 reactions to form isocitrate?

CoA, NAD+, Pyruvate, AMP, & Calcium *These are essentially the reactants that are pushing the process forward

Allosteric activators of pyruvate dehydrogenase include?

Acetyl-CoA, NADH, Fatty Acids, & ATP *These are essentially the products that are causing the process to stop

Allosteric inhibitors of pyruvate dehydrogenase include?

Oxidation/Reduction & Decarboxylation

An oxidative decarboxylation reaction indicates what kind of reactions are taking place?

3 Alpha & 3 Beta subunits

As pertained to ATP synthase, what is the hexameter ring comprised of?

Citrate Synthase Aconitase Isocitrate Dehydrogenase Alpha-Ketoglutarate Dehydrogenase Succinyl-CoA synthetase Succinate Dehydrogenase Fumarase Malate Dehydrogenase

Beginning at the merge between Acetyl CoA & Oxaloacetate, what are the enzymes of the citric acid cycle (Krebs Cycle)?

Citrate Isocitrate Alpha-Ketoglutarate Succinyl-CoA Succinate Fumarate Malate Oxaloacetate

Beginning at the merge between Acetyl CoA & Oxaloacetate, what are the steps of the citric acid cycle (Krebs Cycle)?

(B) Deamination of Nucleic Acids Fatty Acid Oxidation, catabolizing Amino Acids into Ketones, and both Alcohol and Acetaldehyde Dehydrogenase can lead to Acetyl-CoA.

Clearly, Acetyl-CoA can be formed in ways other than by Pyruvate Dehydrogenase. Which of the following is NOT a way Acetyl-CoA can be formed? (A) Fatty Acid Oxidation(B) Deamination of Nucleic Acids(C) Amino Acid catabolism into Ketones(D) Alcohol and Acetaldehyde Dehydrogenase

Synthases and Synthetases both catalyze synthesis reactions.Synthases do not require outside energy to catalyze their reactions, whereas Synthetases do need outside energy to catalyze their reactions (usually in the form of GTP or ATP).

Compare syntheses and synthetases.

(1) Glycolysis - 2 ATP, and 2 NADH (2) The Linking Step (Pyruvate Dehydrogenase) - 2 NADH (3) Kreb's Cycle - 2 GTP [similar to ATP], 6 NADH, and 2 FADH2In total: 4 ATP/GTP, 10 NADH, 2 FADH2

During each stage of cellular respiration, state how many net ATP/GTP, NADH, and FADH2 molecules are produced per molecule of glucose? (1) Glycolysis (2) The Linking Step (Pyruvate Dehydrogenase) (3) Kreb's Cycle

(B) 1, 2 During the linking step, one pyruvate loses 1 of its carbons as CO2. During the Kreb's cycle, one pyruvate loses 2 of its carbons as CO2.

During glycolysis, glucose is broken in half, forming 2 pyruvate molecules. Then during the linking step, one pyruvate loses ___ of its carbons as CO2. During the Kreb's cycle, one pyruvate loses ___ of its carbons as CO2. (A) 1, 1(B) 1, 2(C) 0, 3(D) 2, 1

(C) H2O O2 is reduced into H2O via the following reaction during the electron transport chain:2e- + 2H+ + 1/2O2 --> H2O

During the electron transport chain, NADH is oxidized to NAD+, resulting in the formation of electrons. Those electrons are then used to convert O2 into: (A) CO2(B) ROS(C) H2O(D) CO

(B) oxidized, acetyl-CoA During the linking step (pyruvate dehydrogenase), pyruvate is oxidized and becomes acetyl-CoA.

During the linking step (pyruvate dehydrogenase), pyruvate is _______________ and becomes ______________. (A) oxidized, oxaloacetate(B) oxidized, acetyl-CoA(C) reduced, oxaloacetate(D) reduced, acetyl-CoA

Oxalosuccinate

During the oxidation of isocitrate, the intermediate that is decarboxylated to form α-ketoglutarate is _______________.

True

Everything in the Krebs cycle is an enzyme-catalyzed reaction (True/False)

2

For every FADH2, how many ATPs are indirectly formed?

3

For every NADH, how many ATPs are indirectly formed?

Nucleoside Diphosphokinase

GTP + ADP --> GDP + ATP. This formation of ATP is catalyzed by which enzyme?

C) Cytoplasm

Glycolysis occurs in the: A) Mitochondria B) Nucleus C) Cytoplasm D) None of the above

(B) organism, cell Hormonal Regulation is focused on meeting the energy needs of the organism. Allosteric regulation substrate availability are focused on meeting the energy needs of the cell.

Hormonal Regulation is focused on meeting the energy needs of the ______________. Allosteric regulation substrate availability are focused on meeting the energy needs of the _______________. (A) organism, muscles(B) organism, cell(C) cell, organism(D) cell, muscles

3 [E1,E2,E3]

How many enzymes does the pyruvate dehydrogenase complex have?

If ATP levels are high, that indicates that the cell already has enough energy; thus, it should slow down the production of that energy by inhibiting pyruvate dehydrogenase, which will in turn slow down the citric acid cycle since acetyl-CoA is required for it to run.

If ATP levels are high, why would it be in the cell's best interest to inhibit pyruvate dehydrogenase?

If Acetyl-CoA levels are high, this means that the Krebs Cycle has slowed down (probably due to reduced Oxygen levels), and the Acetyl-CoA could not actually be used to produce ATP.

If Acetyl-CoA levels are high, why would it be in the cell's best interest to inhibit Pyruvate Dehydrogenase? Where will the Acetyl-CoA be used?

High levels of calcium result from muscle contraction, which is a process that requires energy. To get more energy, the cell will want to ramp up the linking step and the Kreb's cycle by activating pyruvate dehydrogenase.

If calcium levels are high, why would it be in the cell's best interest to activate pyruvate dehydrogenase?

The pyruvate dehydrogenase reaction produces acetyl-CoA which is used to build up fatty acids. If there is already a high level of fatty acids, the cell will try and decrease the level of acetyl-CoA by inhibiting pyruvate dehydrogenase

If fatty acid levels are high, why would it be in the cell's best interest to inhibit pyruvate dehydrogenase?

It undergoes aerobic cell respiration, leading into the Krebs cycle

If oxygen is present, what happens to the products of glycolysis?

A) CO2

If the Krebs cycle is overstimulated, what molecule would be overproduced? A) CO2 B) O2 C) GDP D) NAD+

A) Tense conformation

In this conformation state, the ADP and Pi are brought close enough so that they can be combined to form the ATP within the beta subunit of ATP synthase A) Tense conformation B) Open conformation C) Loose conformation

C) Loose conformation

In this conformation state, the bound ADP and Pi become trapped and cannot leave the beta subunit of ATP synthase A) Tense conformation B) Open conformation C) Loose conformation

ATP synthase

Large protein that uses energy from H+ ions to bind ADP and a phosphate group together to produce ATP

Oxidative Phosphorylation

Part of the electron transport chain. A process occurring in the mitochondria that results in the formation of ATP from the flow of electrons across the inner membrane to bind with oxygen.

(B) the production of ATP

Pyruvate dehydrogenase is a multienzyme complex that catalyzes a series of reactions. Which of the following is not carried out by pyruvate dehydrogenase? a) a decarboxylation reaction b) the production of ATP c) producing an acetyl group from pyruvate d) combining the acetyl group with a cofactor

Allosteric

Pyruvate dehydrogenase regulation is considered to be _______ regulation

- CoA - Activator - NADH - Inihibitor - ATP - Inihibitor - NAD+ - Activator - Fatty Acids - Inihibitor - Pyruvate - Activator - AMP - Activator - Ca2+ - Activator - Acetyl-CoA - Inihibitor Rule of thumb is to remember that typically a substrate will act as an activator and a product will act as an inhibitor.

State whether each of the following molecules is an allosteric activator or inhibitor of pyruvate dehydrogenase:- CoA- NADH- ATP- NAD+- Fatty Acids- Pyruvate- AMP- Ca2+- Acetyl-CoA

Proton pump

The F0 region of the ATP synthase is considered to be what?

Catalytic unit

The F1 region of ATP synthase, consisting of Alpha, beta, gamma, epsilon, & delta subunits, is considered what type of unit?

B) Inner mitochondrial matrix

The Krebs Cycle occurs in the: A) Cytoplasm B) Inner mitochondrial matrix C) Outer mitochondrial membrane D) Nucleus

A) Inner membrane of the mitochondria

The complexes of the electron transport chain are found in the: A) Inner membrane of the mitochondria B) Outer membrane of the mitochondria C) Matrix of the mitochondria

(A) Increase ATP production There is an increased ATP production, if the levels of hydrogen ions increase in the inter-membrane space of the mitochondria.

The effect of increased levels of hydrogen ions in the inter-membrane space of the mitochondria is a) Increase ATP production b) Decreased levels of oxidative phosphorylation c) Increased levels of water in inter-membrane space d) Decreased levels of chemiosmosis

Redox, dehydration, hydration, and decarboxylation reactions

The eight steps of the citric acid cycle are a series of what 4 types of reactions?

Substrate Phosphorylation

The formation of ATP by directly transferring a phosphate group to ADP from an intermediate substrate in catabolism. *Happens in Glycolysis & Krebs Cycle

D) Endergonic Step 2: +6.3kJ Step 8: +29.7kJ = Highly Endergonic

The last step of the citric acid cycle from Malate back to Oxaloacetate and the second step from Citrate to Isocitrate requires energy, meaning they are both ____ reactions A) Unstable B) Stable C) Exergonic D) Endergonic

Binding Change Mechanism

The mechanism whereby the subunits of ATP synthase adopt three successive conformations to convert ADP + Pi to ATP as driven by the dissipation of the transmembrane proton gradient

Acidic

The more hydrogen concentration, the more ____ a solution is

Basic

The more hydroxide concentration, the more ____ a solution is

Phosphorylation

The pyruvate dehydrogenase complex becomes inactive when it goes through a covalent modification process known as?

Hydrolysis Reaction

The second step in which CoA is released and Citrate is formed is considered what type of reaction?

Pyruvate Decarboxylation

The stage of aerobic cellular respiration that comes after glycolysis. Occurs on the way to the mitochondrial matrix. Pyruvate is oxidized into 1 CO2, 1 NADH, 1 acetyl-COA (2 carbons attached to coenzyme A). What is this preparation step into the Krebs cycle called?

Aldol condensation

The step in which Citryl CoA is formed from Acetyl CoA is considered what type of reaction?

Rate of the reaction

The step in which the alpha-ketoglutarate is formed in the citric acid cycle is the step that determines the?

High energy & unstable

The thioester bond is considered to be?

Cytochrome C

This is a small, water-soluble protein that transfers electrons between complex 3 & 4

Pyruvate Dehydrogenase [E1]

This pyruvate dehydrogenase complex enzyme catalyzes the redox-decarboxylation reaction of pyruvate

Dihydrolipoyl Transacetylase [E2]

This pyruvate dehydrogenase complex enzyme catalyzes the transfer of the acetyl group to CoA

Dihydrolipoyl Dehydrogenase [E3]

This pyruvate dehydrogenase complex enzyme reforms the oxidized version of lipoamide & generates NADH

False. Fatty acids can be converted into acetyl-CoA, and used to make ATP via the Kreb's Cycle and ETC, but acetyl-CoA cannot be converted back into pyruvate. For this reason, fatty acids are not able to contribute to gluconeogenesis.

True or False. Fatty acids are a crucial during a state of hypoglycemia because they can be converted into glucose via gluconeogenesis.

False. Succinate Dehydrogenase can be considered a Flavoprotein because it is covalently bound to FAD.

True or false? Fumarate can be considered a Flavoprotein because it is covalently bound to FAD.

Two, One

Ubiquinol (QH2) is able to hold ____ electron(s), while Cytochrome C can only hold ____ electron(s)

Used by G proteins & to form ATP

What are 2 main functions of the GTP in the citric acid cycle?

1. Entry into the citric acid cycle 2. Produce fatty acids when ATP is high

What are the 2 main purposes of Acetyl-CoA?

Tense, Open & Loose

What are the 3 conformational states of the beta subunits of the ATP synthase in the F1 region?

NADH dehydrogenase (NADH oxidoreductase) Succinate Reductase Cytochrome C Oxidoreductase Cytochrome C Oxidase

What are the 4 complexes in the electron transport chain in order from 1-4?

Pyruvate Dehydrogenase [E1] Dihydrolipoyl Transacetylase [E2] Dihydrolipoyl Dehydrogenase [E3]

What are the enzymes of the pyruvate dehydrogenase complex?

C) 2 ATP, 6 NADH, 2 FADH2, & 4 CO2 Answer Choice B is 1 cycle of Krebs Cycle, but it has 2 cycles making C the correct answer.

What are the final products of the Citric acid cycle, not including the preparatory phase between it and glycolysis? (Remember, there are 2 molecules of pyruvate formed, so Krebs cycle has 2 cycles) A) 1 ATP, 3 NADH, 2 FADH2, & 1CO2 B) 1 ATP, 3 NADH, 1 FADH2, & 2 CO2 C) 2 ATP, 6 NADH, 2 FADH2, & 4 CO2 D) 4 ATP, 3 NADH, 2 FADH2, & 4 CO2

C Ring & Gamma Subunit

What are the only two parts of the ATP synthase that is actually taking part in rotating the molecule?

1. Synthesis 2. Isomerization 3. Oxidative Decarboxylation 4. Oxidative Decarboxylation 5. GTP synthesis 6. Redox Reaction 7. Hydration 8. Redox Reaction

What are the reactions of each step in the citric acid cycle?

Succinate dehydrogenase

What enzyme of the TCA cycle also acts as complex II of the ETC & is bound to the inner mitochondrial membrane?

It is NOT a proton pump, whereas the other 3 complexes move hydrogen ions from the matrix to the inner membrane of the mitochondria

What is the difference in complex 2 of the electron transport chain to the other 3?

Complex 1: its vertical end lies in the matrix of the mitochondria

What is the only complex in the electron transport chain that lies in the matrix of the mitochondria?

B) Open conformation

What is the only conformation state that participates in the releasing of the ATP of the beta subunits of the ATP synthase? A) Tense conformation B) Open conformation C) Loose conformation

B) Beta

What is the only subunit in the F1 region of the ATP synthase that actually participates in releasing ATP? A) Alpha B) Beta C) Gamma D) Delta E) Epsilon

ADP:ATP

What ratio alerts the body when it's in need of more energy through the electron transport chain?

The citric acid cycle will speed up since the alpha-ketoglutarate, a key substrate for the citric acid cycle, is now more available.

What will happen to the activity of the citric acid cycle when amino acids are being broken down into alpha-ketoglutarate?

The citric acid cycle will slow down since the substrates of acetyl-CoA and citrate are not as available anymore.

What will happen to the activity of the citric acid cycle when citrate is shuttled out of the mitochondrial matrix in an effort to carry acetyl-CoA to the site for fatty acid synthesis?

Negative Delta G Value

When a process is irreversible, what type of G value is obtained?

Irreversible

When going from the product of glycolysis, pyruvate, into the citric cycle with acetyl-CoA, it is considered a(n) [irreversible/reversible] reaction.

(C) Mitochondria

Where does oxidative phosphorylation take place? a) Ribosomes b) Nucleus c) Mitochondria d) Cell membrane

(D) Mitochondrial Matrix The majority of the Kreb's cycle is carried out in the mitochondrial matrix of eukaroytic cells.

Where is the majority of the Kreb's cycle carried out in the mitochondria of eukaroytic cells? (A) Outer Membrane(B) Inner Membrane(C) Intermembrane Space(D) Mitochondrial Matrix

L-isomer

Which malate isomer is formed in the citric acid cycle?

(1) Citrate synthase - ADP (2) Isocitrate dehydrogenase - ADP and Ca2+ (3) Alpha-ketoglutarate dehydrogenase - Ca2+

Which of the following are allosterically activated by ADP? Ca2+? Both? (1) Citrate synthase(2) Isocitrate dehydrogenase(3) Alpha-ketoglutarate dehydrogenase

(1) Citrate synthase - NADH, ATP, Citrate, and Succinyl-CoA (all of them because it is the starting point for the citric acid cycle) (2) Isocitrate dehydrogenase - NADH and ATP. (3) Alpha-ketoglutarate dehydrogenase - NADH and succinyl-CoA

Which of the following are allosterically inhibited by NADH? ATP? Citrate? Succinyl-CoA? (1) Citrate synthase(2) Isocitrate dehydrogenase(3) Alpha-ketoglutarate dehydrogenase

(B) I and II only Each of the following are cofactors used by Pyruvate Dehydrogenase:I. CoA and Thiamine PyrophosphateII. Lipoic acid and FADIII. NAD+ only

Which of the following are pairs of cofactors used by Pyruvate Dehydrogenase? I. CoA and Thiamine PyrophosphateII. Lipoic acid and FADIII. NAD+ and NADP (A) I only(B) I and II only(C) II and III only(D) I, II and III

(D) I, II, and III Sugars, proteins, and fats can all be interconverted into acetyl-CoA, which can then enter the Kreb's cycle and generate energy. Acetyl-CoA connects many of the metabolic pathways together, making it a very important intermediate.

Which of the following biomolecules can be converterted into acetyl-CoA?I. SugarsII. FatsIII. Proteins (A) I Only(B) I and II Only(C) I and III Only(D) I, II, and III

(D) Oxaloacetate Pyruvate is converted to Oxaloacetate to enter Gluconeogenesis.

Which of the following molecules would Pyruvate be directly converted to in order to enter Gluconeogenesis? (A) Glycerol(B) Citrate(C) Acetyl CoA(D) Oxaloacetate

(A) III only Each of the following statements about Citrate are true:I. The Thioester bond in Acetyl-CoA is hydrolyzed, providing the energy to drive Citrate Synthesis.II. The two carbons from the Acetyl-CoA are incorporated into Citrate's 6 Carbons.III. The two carbons Citrate acquired from Acetyl-CoA will leave the TCA cycle as Carbon Dioxide.

Which of the following statements about forming Citrate are true? I. The Ester bond in Acetyl-CoA is hydrolyzed, providing the energy to drive Citrate Synthesis.II. The two carbons from the Acetyl-CoA are incorporated into Citrate's 5 Carbons.III. The two carbons Citrate acquired from Acetyl-CoA will leave the TCA cycle as Carbon Dioxide. (A) III only(B) I and II only(C) II and III only(D) I, II and III

Step 6: Succinate to Fumarate

Which step(s) involves the formation of FADH2 in the citric acid cycle & is the only step that is neither exergonic/endergonic, but in equilibrium?

Steps 3: Isocitrate to Alpha-Ketoglutarate 4: Alpha-Ketoglutarate to Succinyl-CoA 8: Malate to Oxaloacetate

Which step(s) involves the formation of NADH in the citric acid cycle?

Step 5: Succinyl -CoA to Succinate

Which step(s) involves the formation of a high energy molecule GTP in the citric acid cycle?

Citrate synthase, isocitrate dehydrogenase, and alpha-ketoglutarate dehydrogenase are allosterically regulated, controlling the citric acid cycle.

Which three enzymes of the citric acid cycle are the primary site for allosteric regulation of the citric acid cycle?

Glycolysis is only needed when you are using glucose for energy. The Kreb's cycle on the other hand is needed for the utilization of sugars, fats, or amino acids for energy. Because cells need energy basically all the time, they will at least want the Kreb's cycle turned on to some degree or another.

Why is it that glycolysis can be completely turned off while Kreb's cycle is usually turned on to one degree or another?

The Kreb's cycle is not regulated via hormones because the Kreb's cycle will always be turned on whether an individual is in the fed or fasted state.

Why is it that the Kreb's cycle is not regulated via hormones?

Enol

With an aldol condensation reaction, the intermediate formed will be an ____ molecule

Citryl CoA

what is the intermediate of acetyl CoA and oxaloacetate to citrate?