Ch 10 - Carbohydrate Metabolism II: Aerobic Respiraiton Flashcards

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1
Q

Where does the citric acid cycle take place and what is its main purpose?

A
  • occurs in the mitochondrial matrix

- to oxidize carbons in intermediates to CO2 and generate high-energy electron carriers (NADH and FADH2) and GTP

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2
Q

What does citrate synthase do in the citric acid cycle?

A
  • couples acetyl-CoA to oxaloacetate and then hydrolyzes the resulting product, forming citrate and CoA-SH
  • regulated by negative feedback from ATP, NADH, succinyl-CoA, and citrate
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3
Q

What does aconitase do in the citric acid cycle?

A

isomerizes citrate to isocitrate

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4
Q

What does isocitrate dehydrogenase do in the citric acid cycle?

A
  • oxidizes and decarboxylates isocitrate to form alpha-ketoglutarate
  • this enzyme generates the first CO2and the first NADH of the cycle
  • as the rate limiting step of the citric acid cycle, it is heavily regulated: ATP and NADH are inhibitors; ADP and NAD+ are activators
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5
Q

What does alpha-ketoglutarate dehydrogenase complex do in the citric acid cycle?

A
  • acts similarly to PDH complex, metabolizing alpha-ketoglutarate to form succinyl-CoA
  • this enzyme generates the second CO2 and second NADH of the cycle
  • inhibited by ATP, NADH, and succinyl-CoA
  • activated by ADP and Ca2+
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6
Q

What does succinyl-CoA synthetase do in the citric acid cycle?

A
  • hydrolyzes the thioester bond in succinyl-CoA to form succinate and CoA-SH
  • generates the one GTP generated in the cycle
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7
Q

What does succinate dehydrogenase do in the citric acid cycle?

A
  • oxidizes succinate to form fumarate
  • this flavoprotein is anchored to the inner mitochondrial membrane because it requires FAD, which is reduced to form one FADH2 generated in the cycle
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8
Q

What does fumarase do in the citric acid cycle?

A

hydrolyzes the alkene bond of fumarate, forming malate

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9
Q

What does malate dehydrogenase do in the citric acid cycle?

A
  • oxidizes malate to oxaloacetate

- generates the third and final NADH of the cycle

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10
Q

Where does the electron transport chain take place and what happens in the the chain?

A
  • on the matrix facing surface of the inner mitochondrial membrane
  • NADH donates electrons to the chain, which are passed from one complex to the next
  • as the ETC progresses, reduction potentials increase until oxygen, which has the highest reduction potential, receives the electrons
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11
Q

What does Complex I (NADH-CoQ oxidoreductase) of the ETC do and how many protons are translocated?

A
  • uses an iron-sulfur cluster to transfer electrons from NADH to flavin mononucleotide (FMN), and then to coenzyme Q (CoQ), forming CoQH2
  • 4 protons are translocated y Complex I
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12
Q

What does Complex II (Succinate-CoQ oxidoreductase) of the ETC do and how many protons are translocated?

A
  • uses an iron sulfur cluster to transfer electrons from succinate to FAD, and then to CoQ, forming CoQH2
  • no proton pumping occurs at complex II
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13
Q

What does Complex III (CoQH2-cytochrome c oxidoreductase) of the ETC do and how many protons are translocated?

A
  • uses an iron-sulfur cluster to transfer electrons from CoQH2 to heme, forming cytochrome c as part of the Q cycle
  • 4 protons are translocated by complex III
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14
Q

What does Complex IV (cytochrome c oxidase) of the ETC do and how many protons are translocated?

A
  • uses cytochromes and Cu2+ to transfer electrons in the form of hydride ions (H-) from cytochrome c to oxygenk, forming water
  • 2 protons are translocated by complex IV
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15
Q

What is required since NADH cannot cross the inner mitochondrial membrane?

A

one of 2 available shuttle mechanisms to transfer electrons in the mitochondrial matrix must be used: glycerol 3-phosphate and the malate-aspartate shuttle

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16
Q

How is the glycerol 3-phosphate shuttle used?

A
  • electrons are transferred from NADH to DHAP, forming glycerol 3-phosphate
  • these electrons can then be transferred to mitochondrial FAD, forming FADH2
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17
Q

How is the malate-aspartate shuttle used??

A
  • electrons are transferred from NADH to oxaloacetate, forming malate
  • malate can then cross the inner mitochondrial membrane and transfer the electrons to mitochondrial NAD+, forming NADH
18
Q

What is the proton-motive force?

A
  • the electrochemical gradient generated by the electron transport chain across the inner mitochondrial membrane
  • the intermembrane space has a higher concentration of protons than the matrix
  • this gradient stores energy, which can be used to form ATP via chemiosmotic coupling
19
Q

What is ATP synthase?

A

the enzyme responsible for generating ATP from ADP and an inorganic phosphate (Pi)

20
Q

What is the difference between the F0 portion and the F1 portion?

A
  • F0: an ion channel, allowing protons to flow down the gradient from the intermembrane space to the matrix
  • F1: uses the energy released by the gradient to phosphorylate ADP into ATP
21
Q

What are the products of glycolysis?

A

2 NADH to 2 ATP

22
Q

What are the products of pyruvate dehydrogenase?

A
  • pyruvate dehydrogenase generates 1 NADH per molecule of pyruvate
  • because each glucose forms 2 molecules of glucose, this complex produces a net of 2 NADH
23
Q

What are the products of the citric acid cycle?

A

cycle generates 3 NADH, 1 FADH2, and 1 GTP (6 NADH, 2 FADH2, and 2 GTP per molecule of glucose)

24
Q

What does each NADH and FADH2 yield?

A
  • NADH yields 2.5 ATP; 10 NADH form 25 ATP

- FADH2 yields 1.5 ATP; 2 FADH2 form 3 ATP

25
Q

What are GTP converted to?

A

ATP

26
Q

How many ATP molecules are made per glucose?

A
  • 2 ATP from glycolysis + 2 ATP (GTP) from citric acid cycle + 25 ATP from NADH + 3 ATP from FADH2 = 32 (optimal)
  • inefficiencies of the system and variability between cell makes 30-32 ATP/glucose the commonly accepted range for energy yield
27
Q

What is the overall reaction of the pyruvate dehydrogenase complex?

A

pyruvate + CoA-SH + NAD+ –> acetyl-CoA + CO2 + NADH + H+

28
Q

What other molecules can be used to make acetyl-CoA and how does the body perform this conversion for each?

A
  • fatty acids: shuttle acyl croup from cytosolic CoA-SH to mitochondrial CoA-SH via carnitine; then undergo beta oxidation
  • ketogenic amino acids: transaminate to lose nitrogen; convert carbon skeleton into ketone body, which can be converted into acetyl-CoA
  • ketones: revers a ketone body formation
  • alcohol: alcohol dehydrogenase and acetaldehyde dehydrogenase convert alcohol into acetyl-CoA
29
Q

What are dehydrogenases?

A
  • a subtype of oxidoreductases (enzymes that catalyze a redox reaction
  • transfer a hydride ion (H-) to an electron acceptor, usually NAD+ or FAD
  • lookout for a high energy electron carrier being formed
30
Q

What is the main difference between citrate and succinyl-CoA synthases regarding bonding?

A
  • citrate does not require energy input in order to form covalent bonds, but succinyl does
31
Q

What are the substrates of the citric acid cycle?

A
Please, Can I Keep Selling Seashells For Money, Officer?
Pyruvate
Citrate
Isocitrate
alpha-Ketoglutarate
Succinyl-CoA
Succinate
Fumarate
Malate
Oxaloacetate
32
Q

What is the purpose of all the reactions that collectively make up the citric acid cycle?

A
  • complete oxidation of carbons in intermediates to CO2 so that reduction reactions can be coupled with CO2 formation, thus forming energy carriers such as NADH and FADH2 for the electron transport chain
33
Q

What enzyme catalyzes the rate limiting step of the citric acid cycle?

A

isocitrate dehydrogenase

34
Q

What are the 3 main sites of regulation within the citric acid cycle? What molecules inhibit and activate the 3 main checkpoints?

A
  • citrate synthase: inhibited by ATP, NADH, succinyl-CoA, citrate; no activators
  • isocitrate dehydrogenase: inhibited by ATP and NADH; activated by ADP and NAD+
  • alpha-ketoglutarate complex: inhibited by ATP, NADH, succinyl-CoA; activated by ADP and Ca2+
35
Q

What role does the electron transport chain play in the generation of ATP?

A

ETC generates the proton-motive force, an electrochemical gradient across the inner mitochondrial membrane, which provides the energy for ATP synthase to function

36
Q

Based on its needs, which of the 2 shuttle mechanisms is cardiac muscle most likely to utilize?

A

malate aspartate; more efficient, makes sense for highly aerobic organ such as the heart to utilize in order to maximize its ATP yield

37
Q

What is the difference between ETC and oxidative phosphorylation? What links the 2?

A
  • the ETC is made up of physical set of intermembrane proteins located in the inner mitochondrial matrix, and they undergo redox reactions as they transfer electrons to oxygen, the final electron acceptor
  • as electrons are transferred, a proton-motive force is generated in the intermembrane space
  • oxidative phosphorylation is the process by which ATP is generated via harnessing the proton gradient, and it utilizes ATP synthases to do so
38
Q

What is the main difference between TCA cycle and glycolysis for carbohydrate metabolism?

A

TCA requires oxygen, glycolysis enzymes can function under anaerobic conditions

39
Q

What would be expected if a patient has been exposed to a toxic compound that increases permeability of mitochondrial membranes to protons?

A
  • the increase allows the proton-motive force to be dissipated through locations besides F0 portion of ATP synthase
  • ATP synthase is less active and forming less ATP
  • the body will attempt to regenerate the proton-motive force by increasing fuel catabolism
  • the increase in fuel use requires more oxygen utilization in the ETC
40
Q

What form do fatty acids enter the catabolic pathway?

A

acetyl-CoA

41
Q

Why can cytosolic NADH yield potentially less ATP than mitochondrial NADH?

A

electrons can use more than one pathway - one of which loses energy that could be used for ATP synthesis - that account for the potential decreased yield of ATP (shuttles)

42
Q

What directly provides the energy needed to form ATP in the mitochondria?

A

the electrochemical gradient (proton-motive force) directly drives the phosphorylation of ATP by the F1 portion of ATP synthase