L11: TCA Cycle and Oxidative Phosphorylation Flashcards

1
Q

anaerobic glycolysis

A
  • low energy production

- pyruvate -> lactate

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2
Q

TCA cycle and oxidative phosphorylation

A
  • high energy production

- pyruvate -> acetyl CoA -> TCA cycle

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3
Q

acetyl CoA as key molecule

A
  • multiple fuel sources:
    • glucose
    • amino acids
    • ketones
    • pyruvate
    • fatty acids
    • acetate
    • ethanol
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4
Q

coenzyme A

A
  • used in energy production and fatty acid synthesis
  • sulfur containing molecule that is usually coupled to a 2C acetyl group or acyl group
  • has high energy transfer potential
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5
Q

TCA cycle occurs where

A
  • mitochondrial matrix
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6
Q

ETC and ATP synthase are located where

A
  • inner mitochondrial membrane
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7
Q

pyruvate -> acetyl CoA catalyzed by

A
  • pyruvate dehydrogenase complex
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8
Q

pyruvate dehydrogenase complex

A
  • consists of 3 distinct enzymes and 5 coenzymes
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9
Q

PDC cofactors

A
  • thiamine pyrophospahte (B1)
  • lipoic acid (inhibited by arsenic)
  • FAD (B2; riboflavin)
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10
Q

PDC coenzyme substrates

A
  • CoA (B5; pantothenic acid)

- NAD+ (B3; niacin)

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11
Q

where is pyruvate transported for the PDC

A
  • mitochondrial matrix
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12
Q

Leigh disease symptoms

A
  • severe neurological disorder
  • muscle weakness
  • difficulty breathing
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13
Q

Leigh disease results

A
  • damage to the brainstem, cerebellum, and basal ganglia
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14
Q

Leigh disease cause

A
  • deficiencies in PDC
  • lactic acidosis
  • deficit in mitochondrial energy production - disruptive to brain function
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15
Q

First step of TCA

A
  • oxaloacete -> citrate
  • addition of acetyl-CoA from PDC
  • via citrate synthesis
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16
Q

second step of TCA

A
  • citrate to isocitrate

- via aconitase

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17
Q

third step of TCA

A
  • isocitrate to alpha-ketoglutarate
  • via isocitrate dehydrogenase
  • generates NADH H+ and CO2
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18
Q

fourth step of TCA

A
  • alpha ketoglutarate -> succinyl CoA
  • via alpha ketoglutarate dehydrogenase
  • produce NADH, H+, and CO2
  • add back CoASH
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19
Q

fifth step of TCA

A
  • succinyl CoA -> succinate
  • via succinate thiokinase
  • will generate GTP and get rid of CoASH
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20
Q

sixth step of TCA

A
  • fumarate -> malate

- via fumarase

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21
Q

seventh step of TCA

A
  • malate to oxaloacetate
  • via malate dehydrogenase
  • will generate NADH and H+
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22
Q

amino acid precursors

A
  • oxaloacetate

- alpha-ketoglutarate

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23
Q

neurotransmitter precursors

A
  • glutamate -> GABA

- derived from alpha ketoglutarate

24
Q

porphyrin precursors

A
  • heme

- derived from succinyl-CoA

25
Q

fatty acid precursors

A
  • derived from citrate
26
Q

glucose precursors

A
  • derived from malate
27
Q

anaplerotic reactions

A
  • if TCA intermediates are removed from the cycle, oxaloacetate must be provided by alternative means
28
Q

alternative means of getting oxaloacetate

A
  • replenished by conversion from pyruvate via pyruvate carboxylase
    • uses ATP
  • can enter via amino acid degradation at
    • pyruvate
    • glutamate -> succinate
    • succinyl CoA
    • fumarate
    • oxaloacetate
  • odd chain fatty acids and branch chain amino acids enter as succinyl coA through a propionyl CoA intermediate
29
Q

control points of TCA

A
  • citrate synthase
  • isocitrate dehydrogenase
  • alpha ketoglutarate dehydrogenase
  • malate dehydrogenase
30
Q

citrate synthase nhibited by

A
  • citrate
31
Q

citrate synthase activated by

A
  • oxaloacetate
32
Q

isocitrate dehydrogenase activated by

A
  • ADP

- Ca2+

33
Q

isocitrate dehydrogenase inhibited by

A
  • ATP

- NADH

34
Q

when energy status is high with citrate

A
  • citrate accumulates and halts glycolysis and shunts acetyl CoA towards fatty acid synthesis
35
Q

alpha ketoglutarate dehydrogenase activated by

A
  • Ca2+
36
Q

alpha ketoglutrate dehydrogenase inhibited by

A
  • NADH
  • succinyl CoA
  • ATP
37
Q

when energy status is high with alpha ketoglutarate

A
  • alpha ketoglutarate accumulates and is used in generating amino acids and nucleotide bases
38
Q

malate dehydrogenase inhibited by

A
  • NADH
39
Q

PDC regulation in resting muscle

A
  • energy status high and energy demands are low
  • products like NADH, acetyl CoA, and ATP activate PDKinase to phosphorylate PDC
    • inactivates PDC
40
Q

PDC regulation in exercising muscle

A
  • muscle contracting consumes ATP; energy status low
  • ADP and pyruvate inhibit PDKinase
  • Ca2+ levels rise to be used in muscle contraction
    • activates PDPhosphatase
      • removes phosphate from PDC, and activates it
41
Q

ETC process

A
  • Complex I (NADH dehydrogenase)
  • Complex II (succinate dehydrogenase)
  • Coenzyme Q
  • Complex III (cyt c b-c1 complex)
  • Cyt C
  • Complex IV (cyt c oxidase)
42
Q

where does FADH2 drop electrons off?

A
  • succinate dehydrogenase at Complex II
  • doesn’t pump protons itself
  • donates electrons to CoQ and then complex II
43
Q

ETC

A
  • electron transferring flavoprotein

- accepts electrons from fatty acid oxidation and transfers them to CoQ

44
Q

glycerol-3-phosphate dehydrogenase

A
  • shuttle component for reoxidizing NADH
45
Q

proton motive force

A
  • pumping protons out of the matrix creates a:
    • pH gradient
    • charge gradient
  • pushes proteins to re-enter the matrix
  • power ATP synthesis via ATP synthase
46
Q

F0 of ATP synthase?

A
  • in inner mitochondrial membrane

- proton channel

47
Q

F1 of ATP synthase

A
  • in matrix

- catalytic subunit (binding site for ADP and ATP)

48
Q

can ATP synthase form ATP in absence of proton gradient?

A
  • yes!

- but proton flow causes a conformational change that results in release of ATP from the enzyme

49
Q

products from Glycolysis

A
  • 2 ATP

- 2 NADH (*1.5) = 3 ATP

50
Q

products from PDC

A
  • 2 NADH (*2.5) = 5 ATP
51
Q

products from TCA cycle

A
  • 6 NADH (*2.5) = 15 ATP
  • 2 FADH2 (*1.5) = 3 ATP
  • 2 ATP
52
Q

total GTP from glycolysis

A
  • 30 ATP
53
Q

yield on glycolysis

A
  • 30%

- rest released as heat and ion transport

54
Q

why does the NADH from glycolysis yield less ATP?

A
  • it has to be transported/shuttled into the inner mitochondrial membrane and that requires some energy
55
Q

why does FADH2 yield less ATP

A
  • because it enters the ETC has a further spot down the chain.