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MTC > TCA cycle > Flashcards

TCA cycle Flashcards

wk 7

1
Q

How are kinase and phosphatase regulated?

A

Via changes in NADH, acetyl-CoA, pyruvate and Insulin.

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2
Q

How is the pyruvate dehydrogenase complex regulated?

A

Covalent modification using specific kinase and phosphatase

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3
Q

What is covalent modifcation?

A

Where the structure of an enzyme is modified by adding special groups to specific locations. In regulation - the addition of these groups is reversible.

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4
Q

What are the cofactors used in the regulation of pyruvate dehydrogenase

A

Thiamine, Lipoate and FAD+

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5
Q

What are the activator Allosteric regulators of pyruvate Dehydrogenase?

A

F1,6BP

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6
Q

What are the inhibitory Allosteric regulators of pyruvate Dehydrogenase?

A

ACoA

NADH

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7
Q

What are the consequnces of pyruvate Dehydrogenase deficiency?

A
  • Progressive neurodegenerative disease
  • Intermittent ataxia
  • Poor muscle tone
  • Lethargy
  • Seizures
  • Abnormal eye movements
  • Lactate buildup
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8
Q

What are the intermediates of the TCA cycle?

A

Citrate

Isocitrate

A-ketoglutarate

Succinate

Fumarate

Malate

Oxaloacetate

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9
Q

What is the role of anaplerotic reactions

A

replenishes oxaloacetate in the citric acid cycle after been consumed AND maintain adequate levels of ATP to allow for the uninterrupted continuation of cellular respiration.

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10
Q

What are anaplerotic reactions?

A

Chemical reactions that form the intermediates for the TCA cycle.

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11
Q

What is the chemical make-up of Oxaloacetate?

A

an Asparate transaminase

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12
Q

What is the only mitochondrial enzyme capable of ATP production and how?

A

Syccinyl-CoA Synthetase

via substrate level phosphorylation (anaerobic)

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13
Q

What is the role of Syccinyl-CoA Synthetase?

A

conversion of Succinyl CoA –> Succinate

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14
Q

What is Cataplerotic vs anaplerotic

A

C= exit point
A = Entry points

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15
Q

What occurs when there is high ADP?

A

Faster respiration

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16
Q

What occurs when there is low ADP?

A

Slower respiration

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17
Q

How is the rate of respiration controlled?

A

By the amount of ADP

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18
Q

What does electron flow cause?

A

transport of protons from mitochondrial matrix into inner membrane

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19
Q

What does the electron transport chain create?

A

proton concentration gradient

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20
Q

What is chemiosmosis?

A

Process of ATP synthesis using free energy from electrons when they are passed to several carriers

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21
Q

How does the TCA cycle link to glucose oxidation and ATP production?

A

Link reaction connects glycolysis to TCA by creating aCoA

Electron transporters used to generate a proton motive force and generate ATP via chemiosmosis

Oxidative phosphorylation

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22
Q

What are the 5 major exit points of the TCA cycle?

A

Citrate, Ketogluctarate, Succinyl CoA, Malate and OAA

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23
Q

What are the 5 major entry points (anaplerotic reactions)

A

Ketoglutarate, succinyl-CoA, Fumarte, malate and OAA

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24
Q

What is the linking reaction in the TCA cycle?

A

Pyruvate + CoASH + NAD –> CoA + NADH2 + CO2

(occurs twice)

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25
Q

Where does the linking reaction occur?

A

Mitochondrial matrix

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26
Q

How is the linking reaction regulated?

A

Via Allosteric activity and inhibition

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27
Q

What are the components that are allosterically activated involved in linking reaction regulation?

A

NAD+, ADP, Pyruvate, CoASH and Ca

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28
Q

How are active allosteric enzymes activated?

A

by dephosphorylation

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29
Q

What are the allosteric inhibitors involved in regulation of linking reaction?

A

NADH2, acetyl CoA and ATP

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30
Q

How are allosterically inhibited components inhibted?

A

via phosphorylation

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31
Q

What steps in the TCA cycle are regulated?

A

Citrate Synthase, Aconitase, Isocitrate DH, a-KG DH, Succinate DH and malate DH

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32
Q

How is citrate synthase regulated?

A

allosterically activated by citrate.

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33
Q

How is aconite regulated?

A

inhibited by fluroacetate

34
Q

How is Isocitrate DH regulated?

A

Allosteric activated: ADP, NAD, CA

Allosteric inhibited: ATP, NADH2 and Succinyl CoA

35
Q

How is a-KG DH regulated?

A

Allosteric activated: ADP, NAD, CA

Allosteric inhibited: ATP, NADH2 and Succinyl CoA

36
Q

How is Succinate DH regulated?

A

Inhibited by malonate (competitive inhibitor)

37
Q

What is the purpose of the ETC?

A

recycle NADH2 and FADH2 into NAD+ and FAD+

38
Q

What is the site of reactions in the ETC?

A

transmembrane proteins in the inner mitochondria membrane

39
Q

what are the two entry reactions to the ETC?

A

1- NADH2 at complex 1
(NADH-Q reductase) (oxidised to NADH+)

2- FADH2 at complex 2
succinate DH) (oxidised to FAD)

40
Q

What are the 4 large protein complexes for ETC?

A

I = NADH-Q Reductase
II- Succinate Dehydrogenase
III - Cytochrome C Reductase
IV- cytochrome c Oxidase

41
Q

What is the first step in the electron transport chain? (electron movement)

A

NADH2 oxidised at complex I

42
Q

What is the second step in the electron transport chain? (electron movement)

A

Complex I transfers electrons to CoQ

43
Q

What is the third step in the electron transport chain? (electron movement)

A

FADH2 oxidised to FAD+ at complex II

44
Q

What is the fourth step in the electron transport chain? (electron movement)

A

electrons are transferred from CoQ –> cytochrome c –> complex IV

45
Q

What is the fifth step in the electron transport chain? (electron movement)

A

O2 reduced at complex IV

46
Q

What are the four steps that allow the ETC to produce ATP?

A
  1. electron flow causes complexes I-IV to pump protons into intermembrane space
  2. proton movement creates a proton gradient across the inner mitochondrial membrane
  3. protons diffuse down the gradient through an ATP synthase channel
  4. ATP synthase catalyses ATP synthesis
46
Q

How many ATPs synthesised per NADH2?

A

pumps 10 protons = 4 protrons per ATP = 2.5 ATP

46
Q

What is meant by coupling?

A

the electrochemical gradient couples the rate of ETC with the rate of ATP synthesis

46
Q

How many ATPS synthesised per FADH2?

A

pumps 6 protons (4 protons per ATP) = 1.5 ATPs

46
Q

What is uncoupling?

A

ATP synthesises and electron flow is disconnected

electron transport no longer regulated by intact chemiosmotic gradient

47
Q

Where do protons come from?

A

ADP-ATP translocate, H+ pyruvate symporter, shuttles, fatty acid oxidation, NADH2 and FADH@ oxidation and water

47
Q

How does ATP:ADP affect the rate of ETC?

A

decreased ADP:ATP slows down the rate

Increased: speeds it up

48
Q

What are the consequences of uncoupling?

A

increased ADP:ATP = increased electron flow = O2 consumption

increased heat production as energy stored in proton gradient is released.

ATP use greater than formation = metabolic acidosis with compensatory respiratory alkalosis

49
Q
A
50
Q

How does ATP affect ATP synthesis?

A

Respiratory Rate Determines avaliability of O2

51
Q

What is the effect of dinitrophenol?

A

dissipates proton gradient by transporting protons across inner mitochondrial membrane via simple diffusion-mediated transport

52
Q

What is the effect of thermogenin?

A

promotes heat generation (non-shivering thermogenesis)

53
Q

What is thermogenic?

A

Physiological uncoupler (in brown fat)

54
Q

What is the main (general) action of ETC inhibitors?

A

Prevent electrons from being passed from 1 carrier to the next

55
Q

What are the ETC inhibitors?

A

Antimycin
Cyanide and carbon monoxide
ogliomycin
atratyloside
rotenone

56
Q

What is the effect of antimycin?

A

Inhibits the electron transfer from III to Cytochrome C

Inhibits NADH2/FADH2 dependent O use

inhibits ATP synthase

57
Q

What is the effect of cyanide and carbon monoxide?

A

prevents the docking of O2
Inhibits complex IV
Inhibits ATP synthesis

58
Q

What is the effect of oligomycin?

A

Inhibits proton passage through ATP synthase –> proton concentration acts as a barrier to the export of more proteins = decreased electron flow

59
Q

What is the effect of atractyloside?

A

Blocks ADP-ATP transolcase
Cytosolic protons accumulation arrest the ETC
inhibits O2 Consumption

60
Q

What is the effect of Roteone?

A

Inhibits electron transfer from I to CoQ

Restricts NADH2 oxidation

inhibits generation of proton gradient, O2 consumption and ATP synthesis

61
Q

In the TCA cycle, how many ATPS are produced per glucose?

A

32

62
Q

How do cells produce energy in the absence of oxygen?

A

Using lactic acid fermentation (glycolysis alone)

63
Q

What happens to the pyruvate in glycloysis in aerobic conditions?

A

it is converted to acetyl CoA –> enters the TCA –> electrons enter ETC

64
Q

What happens to the pyruvate in glycolysis under anaerobic conditions?

A

Converted into lactate then enters the Cori cycle

65
Q

What does AMPK mean?

A

AMP- activated protein kinase - used to regulate cellular metabolism.

66
Q

What is the role of AMPK in regulation?

A
  1. Shuts off anabolic pathways (ATP using)
  2. Turns on catabolic pathways (ATP making)
67
Q

What factors activate the regulator: AMPK?

A

increased ADP:ATP

increased AMP:ATP

68
Q

What is the mechanism of action for metformin?

A

inhibits complex I → decreased NADH2 oxidation → decreases proton-driven ATP synthesis → increases ADP:ATP and increases AMP:ATP → inhibits glucagon-induced cAMP synthesis and activates AMPK

69
Q

What are the actions of metformin in glycolysis?

A

increased glucose uptake

increased glucose

transporter translocation

increase insulin receptor activity

increase insulin-mediate glucose uptake in skeletal muscle

stimulates glycolytic enzymes

70
Q

What is the role of gluconeogenesis?

A
  • $\downarrow$ uptake of gluconeogenic substrates (alanine, lactate)
  • inhibits gluconeogenic enzymes
  • enhances insulin-mediated suppression of gluconeogenesis
  • opposes the gluconeogenic action of glucagon
71
Q

What does ETC do to NADH2 and FADH2?

A

recycles it back to NAD and FAD

72
Q

What happens to the energy in the ETC?

A

As the electrons are transported along the chain, they lose energy. Some of this energy is conserved by forming a proton gradient in the inner mitochondrial membrane

73
Q

Where does cytochrome carry electrons to?

A

complex IV

74
Q

What carrier picks up electrons from complexes I and II and where does it take them?

A

Ubiquinone Q, takes them to Complex III

75
Q

what does dinitrophenol do?

A

dissipates proton gradient via transport of protons across inner mitochondrial membrane

increased CHO and lipid metabolism

76
Q

What are the ETC inhibitors?

A

Antimycin
cyanide and carrbon monoxide
oligomycin
atractyloside
rotenone

77
Q
A

MTC (14 decks)

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