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Nutrition and Energy > L12 TCA Cycle, ET Chain and Oxidative Phosphorylation > Flashcards

L12 TCA Cycle, ET Chain and Oxidative Phosphorylation Flashcards

1
Q

Describe step 1 of the Krebs Cycle.

Hint: Acetyl CoA - Citrate

A

Acetyl group enters cycle to create citrate and regenerate coenzyme A (CoA).

Enzyme: citrate synthase

Acetyl CoA add its two-carbon fragment to oxaloacetate, a four-carbon compound. Oxaloacetate displaces coA as it attaches to the acetyl group, forming the six-carbon citrate.

CoA is then free to prime another two-carbon fragment derived from pyruvate.

Oxaloacetate is regenerated by the last step of the cycle.

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2
Q

Describe step 2 of the citric acid cycle.

A

Isomerisation of citrate to D-Isocitrate.

A molecule of water is removed and another is added back. The net result is the conversion of citrate to its isomer, isocitrate (still six-carbon molecule).

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3
Q

Describe step 3 of the citric acid cycle.

A

D-isocitrate undergoes oxidative decarboxylation to form alpha-ketoglutarate, NADH and CO2.

Enzyme: isocitrate dehydrogenase

Isocitrate loses a CO2 molecule, and the remaining five-carbon compound is oxidised, reducing NAD+ to NADH. This forms ketoglutarate.

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4
Q

Describe step 4 of the krebs cycle.

A

alpha-ketoglutarate undergoes oxidative decarboxylation alongside the addition of CoA to form succinyl-coA, NADH, H+ and CO2

Enzyme: a-ketoglutarate dehydrogenase

Ketoglutarate loses a CO2; the remaining four-carbon compound is oxidised by the transfer of electrons to NAD+ to form NADH, and is then attached to CoA by an unstable bond. This forms succinyl-CoA.

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5
Q

Describe step 5 of the citric acid cycle.

A

Succinyl-coA involved with substrate level phosphorylation: coA displaced by a phosphate group, which is transferred to GDP, forming GTP. GTP then donates a phosphate group to ADP, to form ATP.

Products: Succinate, CoA and ATP.

Enzyme: Succinyl-CoA synthetase

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6
Q

Describe step 6 of the krebs cycle.

A

Dehydration: Succinate is oxidised to fumarate; two hydrogens are transferred to FAD to form FADH2

Enzyme: succinic dehydrogenase

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7
Q

Describe step 7 of the citric acid cycle.

A

Hydration: Fumarate is converted to malate by addition of water.

Enzyme: fumarase

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8
Q

Describe step 8 of the citric acid cycle.

A

Malate is dehydrogenated to form oxaloacetate and NADH.

Enzyme: malate dehydrogenase

The last oxidative step produces another molecule of NADH and regenerates oxaloacetate, which accepts a two-carbon fragment from acetyl CoA for another turn of the cycle.

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9
Q

How is pyruvate generated?

A

Glycolysis in the cytosol converts glucose to pyruvate.

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10
Q

Where does the citric acid cycle take place?

A

Matrix of the mitochondria

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11
Q

Where does glycolysis take place?

A

Cytosol

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12
Q

What is the role of NADH and FADH2?

A

Act as transporters that carry electrons from glycolysis and the krebs cycle to the electron transport chain.

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13
Q

Where are the electrons sourced from for participation in the electron transport chain?

A

Certain steps in glycolysis and krebs cycle reduce NAD+ and FAD to NADH and FADH2, which carry these electrons (H+) to the electron transport chain.

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14
Q

What happens to pyruvate when oxygen is plentiful?

A

Converted to acetyl CoA for participation in the TCA cycle.

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15
Q

True or false: Red blood cells cannot perform glycolysis.

A

False. RBC’s have cytoplasm but no mitochondria. This means they can perform glycolysis but not TCA cycle.

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16
Q

How does pyruvate enter the mitochondrion?

A

Via transport protein

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17
Q

How is pyruvate converted to acetyl coenzyme A?

A

Three-carbon pyruvate loses a CO2 molecule. The resulting two-carbon molecule is oxidised, losing two hydrogen atoms. One is electron is donated to NAD+, forming NADH and H+.

Coenzyme A is added, forming the two-carbon molecule acetyl coA.

Enzyme: pyruvate dehydrogenase

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18
Q

What is the net gain from glycolysis and the link reaction?

A

2 ATP
4 NADH
2 Acetyl CoA

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19
Q

True or false: Pyruvate dehydrogenase deficiency is a sex-linked disease

A

True

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20
Q

What is the most common feature of pyruvate dehydrogenase deficiency? What symptoms and complications can arise?

A

Lactic acidosis. This causes nausea, vomiting, severe respiratory problems, and cardiac arrhythmia.

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21
Q

Why does lactic acid build up in patients with pyruvate dehydrogenase deficiency?

A

When pyruvate cannot be converted to acetyl coA, NAD+ is regenerated from NADH by reduction of pyruvate to lactate by the enzyme lactate dehydrgenase

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22
Q

Why do neurological problems arise in patients with pyruvate dehdyrogenase deficiency?

A

If pyruvate cannot be converted to acetyl coA, the TCA cycle cannot proceed.

While alternative metabolic pathways are used in an attempt to produce acetyl coA, an energy deficit remains (especially in the CNS). Energy deficit during neural development leads to congenital brain malformation.

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23
Q

From where does the cell obtain acetyl coA for use in the Krebs cycle?

A

Primarily, decarboxylation of pyruvate produced from glycolysis.

Fatty acid and amino acid breakdown also produces acetyl coA.

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24
Q

How many steps in the TCA cycle directly produce ATP?

A

Only one (step 5: succinyl coA to succinate).

However: later on, each NADH makes 3 ATP and each FADH2 makes 2 ATP molecules.

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25
Q

The Krebs cycle produces how many ATP molecules overall?

A

12 (thats 24 per glucose molecule)

3 NADH, each producing 3 ATP = 9

1 FADH2, each producing 2 ATP = 2

1 ATP made by substrate-level phosphorylation = 1

9 + 2 + 1 = 12

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26
Q

How can pyruvate be used to form glucose?

A

Pyruvate can be converted into oxaloacetate by pyruvate carboxylase.

Oxaloacetate can then be made into phosphoenolpyruvate (PEP), which can then form glucose.

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27
Q

Which intermediate from the TCA cycle can be used to form fatty acids and sterols?

A

Citrate

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28
Q

Which intermediate from the Krebs cycle can be used to form Porphyrins and heme?

A

Succinyl-CoA

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29
Q

Which intermediate from the Krebs cycle can be used to form purines?

A

Ketoglutarate

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30
Q

Which intermediate from the TCA cycle can be used to form pyrimidines?

A

Oxaloacetate (first converted to asparagine, then pyrimidines)

31
Q

a-Ketoglutarate can form glutamate. What can subsequently be formed from glutamate?

A

Purines
Glutamine
Proline
Arginine

32
Q

Oxaloacetate is converted into citrate as part of the krebs cycle, but what other molecules can it form??

A

Phosphoenolpyruvate (PEP)

This in turn can be turned into glucose, or:

Serine
Glycine
Cysteine
Phenylalanine
Tyrosine
Tryptophan
33
Q

How many CO2 molecules does Krebs produce from each glucose molecule?

A

4

34
Q

Which enzyme in Krebs allows for substrate level phosphorylation?

A

Succinyl-CoA synthetase

35
Q

Where does Krebs cycle occur?

A

Mitochondrial matrix

36
Q

Why do you breathe out more CO2 after exercise?

A

More turns of TCA cycle = more CO2 produced

37
Q

Which enzymes in Krebs reduce NAD?

A

Isocitrate dehydrogenase

a-Ketoglutarate dehydrogenase

Malate dehydrogenase

38
Q

How is TCA cycle regulated?

A
  1. Substrate availability
  2. Enzyme inhibition by product
  3. Allosteric inhibition
39
Q

How is the TCA cycle regulated by allosteric inhibition?

A

Citrate synthase (inhibited by citrate and ATP)

Isocitrate dehydrogenase (inhibited by NADH and ATP; activated by ADP)

a-Ketoglutarate dehydrogenase (inhibited by NADH and succinyl CoA)

Pyruvate dehydrogenase (inhibited by NADH and acetyl coA. Also regulated by phosphorylation by pyruvate dehydrogenase kinase and phosphatase)

Lots of ATP slows the cycle (need fewer turns) while lots of ADP speeds up cycle.

40
Q

How does arsenic poisoning occur?

A

Arsenic allosterically inhibits pyruvate dehydrogenase, leading to headaches, confusion, diarrhoea and drowsiness.

As poison develops, convulsions and changes to fingernail pigmentation (leukonychia striata) may occur.

Acute symptoms include diarrhoea, vomiting, haematuria, cramps, hair loss, stomach pain, and more convulsions.

41
Q

A 24-year-old woman presents with diarrhoea, dysphagia, jaundice and white transverse lines on the fingernails (Mee’s lines). The patient is diagnosed with arsenic poisoning, that inhibits which of the following enzymes of TCA cycle?

a) Citrate synthase
b) Isocitrate dehydrogenase
c) Pyruvate dehydrogenase
d) Succinate dehydrogenase

A

c) Pyruvate dehydrogenase

42
Q

A biochemistry graduate student isolated all enzymes of TCA cycle to produce NADH, oxidation of which of the following substrates in the citric acid cycle is not coupled to the production of NADH?

a) Succinate
b) Malate
c) a-Ketoglutarate
d) Isocitrate

A

a) Succinate

43
Q

Pyruvate dehydrogenase deficiency is an autosomal recessive disorder and leads to metabolic acidosis. Which of the following accumulates to cause metabolic acidosis?

a) Beta hydroxy butyric acid
b) Acetoacetic acid
c) Fumaric acid
d) Lactic acid

A

d) Lactic acid

44
Q

A 3 year-old child presents with a history of recurrent rash upon sun exposure and passage of purple coloured urine. The child is diagnosed with Congenital Erythropoietic Porphyria, a disorder of pathway of haem biosynthesis. Which of the following intermediates of TCA cycle is used as a precursor for haem biosynthesis?

a) Succinyl coA
b) Acetyl coA
c) Succinate
d) Malate
e) Pyruvate

A

a) Succinyl coA

45
Q

A 2-year-old child was brought to pediatric emergency with convulsions. The child was diagnosed with ammonia intoxication due to some urea cycle disorder. Reduced formation of GABA is considered to be the most important cause of convulsion due to depletion of glutamate from where it is produced by decarboxylation. Which of the following intermediates of TCA cycle is involved in the formation of Glutamate?

a) Succinate
b) Malate
c) a-Ketoglutarate
d) Isocitrate

A

c) a-Ketoglutarate

46
Q

In TCA cycle , GTP is produced at one step by substrate level phosphorylation and that is subsequently utilised for gluconeogenesis. Which of the following enzymes is involved in this process of formation of GTP from GDP?

a) Succinate-coA synthase
b) Succinate dehydrogenase
c) Citrate synthase
d) Isocitrate dehydrogenase

A

a) Succinate-coA synthase

47
Q

A 56-year- old chronic alcoholic has been brought in a semiconscious state to the medical emergency. Blood biochemistry reveals hypoglycemia with blood glucose level of 45 mg/dl. Which of the following intermediates of TCA cycle can be directly converted to phosphoenolpyruvate to trigger the pathway of gluconeogenesis?

a) Succinate
b) Malate
c) a-Ketoglutarate
d) Oxaloacetate
e) Pyruvate

A

d) Oxaloacetate

48
Q

Where does the electron transport chain take place?

A

Inner mitochondrial membrane

49
Q

What is the first protein used in the electron transport chain?

A

NADH dehydrogenase

This protein oxidises NADH produced in the Krebs cycle, resulting in a proton (H+) and NAD+ (remain in the matrix), along with two electrons (bound to the protein).

50
Q

(Regarding the electron transport chain)

After being released from NADH by NADH dehydrogenase, what happens to the two electrons?

A

First they bind to NADH dehydrogenase. Then they are passed between the ETC proteins in a series of redox reactions. As they move they lose energy, some of which is used to pump H+ ions from the matrix into the intermembrane space.

51
Q

What happens to the energy held by the electrons that are passed along the ETC proteins?

A

Some of it is used to pump H+ ions from the matrix to the intermembrane space, the rest is lost as heat.

52
Q

How does a concentration gradient form between the mitochondrial matrix and the intermembrane space during the ETC?

A

As electrons are passed along the ETC proteins, some of their energy is used to pump H+ across from the matrix to the intermembrane space. As the inner mitochondrial membrane is impermeable to H+ ions, a concentration gradient forms.

53
Q

Once the concentration gradient is formed in the electron transport chain, how is ATP produced?

A

H+ ions in the intermembrane space move down their concentration gradient, into the matrix, using protein channels. These are associated with the enzyme ATP synthase, which phosphorylates one ADP for each H+ passing through it.

54
Q

What is ‘chemiosmosis’?

A

The use of energy to generate ATP by the flow of hydrogen ions through ATP synthase, along a chemical gradient.

(Electron transport chain)

55
Q

What is the final protein in the electron transport chain? What does it do?

A

Cytochrome oxidase.

Donates the electron pair to an oxygen atom, which also binds with the hydrogen ions to form water.

56
Q

What is the final electron acceptor in the electron transport chain?

A

Oxygen. Accepts electrons and hydrogens to form water.

57
Q

True or false: In the electron transport chain, the donation of the electrons to the oxygen molecule releases enough energy to regenerate another molecule of ATP

A

True.

The energy released from the electron donation to oxygen is sufficient to pump another H+ ion across the membrane. This can be used to regenerate another ATP.

58
Q

Why does FADH2 regenerate fewer ATP than NADH in the electron transport chain?

A

Although it is also oxidised by the ETC, it interacts with the second protein in the chain (NADH interacts with the first).

This means FADH2 causes less H+ to be pumped into the intermembrane space than NADH, so regenerated less ATP.

59
Q

As electrons pass through the electron transport chain, are the reactions exergonic or endergonic?

A

Exergonic - release energy to pump hydrogen ions across inner membrane.

60
Q

Which of the ETC proteins contain flavin mononucleotides?

A

NADH dehydrogenase

61
Q

Which of the ETC proteins contains an iron-sulphur centre?

A

Cytochrome C reductase

Carrying electrons changes Fe3+ to Fe2+

62
Q

Which of the ETC carriers is a non-protein carrier in the lipid bilayer?

A

Coenzyme Q (ubiquinone)

63
Q

Which of the ETC proteins contains copper?

A

Cytochrome oxidase

Carrying electrons changes Cu2+ to Cu+

64
Q

The electron transport chain can regenerate how many molecules of ATP per glucose molecule?

A

Either 32 or 34

65
Q

NADH produced in glycolysis cannot enter the mitochondria. How do the elections get to the electron transport chain?

A

The NADH molecules made in glycolysis donate electrons to ‘shuttles’ - either malate or glycerol phosphate, depending on there in the body the cell is.

Malate can shuttle 3 ATP molecules, glycerol phosphate can shuttle 2 ATP molecules.

66
Q

Cell in which organs use a malate shuttle to carry electrons from the cytoplasm to the electron transport chain in the mitochondria?

A

Liver, kidneys and heart.

The rest of the body uses glycerol phosphate shuttle (uses FAD rather than NAD as the H acceptor.

67
Q

How many ATPs are produced from substrate level phosphorylation?

A

4

2 from glycolysis, 2 from Krebs cycle.

68
Q

Using malate as the example shuttle, describe how electrons stored in NADH are transported from the cytoplasm to the mitochondria.

A

NADH formed in glycolysis. Oxaloacetate is converted into malate, and as it does so it oxidises NADH, taking the electron and storing it in the malate shuttle.

This process results in NAD+ in the cytoplasm, which is recycled in glycolysis.

The malate shuttle can enter the mitochondria. Once inside, malate is converted back into oxaloacetate, and NAD+ in the matrix is reduced to NADH. This can then be used in the ETC.

Oxaloacetate cannot leave the mitochondria, but it can be converted into aspartate, which can leave. Once in the cytoplasm, aspartate is converted back into oxaloacetate and the process starts again.

69
Q

Although NADH can usually produce more ATP than FADH2, cytosolic NADH is sometime only equally effective. Explain why.

A

In cells that use glycerol phosphate shuttle (i.e. not the liver, kidney, and heart), NADH in the cytosol gives up its two electrons and hydrogen to dihydroxyacetone phosphate (DHAP) forming glycerol-3-phosphate.

G3P shuttles the electrons to the inner mitochondrial membrane to the G3P dehydrogenase protein, which has a FAD group attached. The electrons are transferred to the FAD group, which then carries them to the ubiquinone carrier in the ETC. They enter the ETC at cytochrome reductase, meaning they pump fewer hydrogen ions than mitochondrial NADH molecules can.

70
Q

How many ATPs are yielded during glycolysis, and at which stages?

A

Oxidation of one glucose molecule into two pyruvate molecules = 2 ATP (substrate-level phosphorylation)

Production of 2 NADH and 2H+ = 4-6 ATP

Total from glycolysis = 6-8 ATP

71
Q

How many ATPs are yielded during the link reaction?

A

2 NADH and 2H+ = 6 ATP (oxidative phosphorylation)

Total from link reaction = 6 ATP

72
Q

How many ATPs are yielded during TCA cycle and electron transport chain?

A

Oxidation of succinyl-coA to succinate = 2 GTPs that are converted to ATP (substrate level)

6 NADH and 6 H+ = 18 ATP (oxidative)

2 FADH2 = 4 ATP (oxidative)

Total from Krebs and ETC = 24 ATP

73
Q

How many ATP are yielded from glycolysis, link reaction, TCA cycle and ETC?

A

36-38 ATP per glucose molecule.

Nutrition and Energy (14 decks)

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