10 - TCA and ETC Flashcards

1
Q

What happens straight after pyruvate is formed?

A
  • Pyruvate dehydrogenase (5 enzyme complex) oxidises pyruvate and adds CoA to form Acetyl CoA
  • Occurs in mitochondrial matrix
  • Irreversible loss of CO2 (regulatory step)
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2
Q

If you had a PDH deficiency, e.g due to genetics, what would happen?

A

Lactic acidosis, build up of pyruvate so would be converted to lactate by LDH to produce energy.

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3
Q

Why is Vitamin B important?

A

Produces co-factors, e.g FAD and lipoic acid, that held PDH and therefore keep healthy metabolism

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4
Q

What signals are PDH regulated by?

A
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5
Q

How does the TCA cycle work?

A

2 TCA per glucose

6 NADPH

2 FADH2

2 GTP

(2 CO2)

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6
Q

Summarise the key aspects of TCA

A
  • In mitochondria
  • Central pathway for sugars, FA, KB, AA, Alcohol
  • Oxidative (Acetyl to 2CO2)
  • Produce intermediates that lose CO2 easily to break C-C bonds
  • Does not function in absence of O2
  • Provides precursors for biosynthesis
  • No net synthesis of intermediates
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7
Q

Where does regulation occur in TCA?

A

Isocitrate Dehydrogenase:

+ ADP - NADH, ATP (allosteric)

A-Ketoglutarate Dehydrogenase

  • NADH, ATP, Succinyl CoA
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8
Q

Give some examples of how TCA products act as biosynthetic precursors.

A

C5/C4 - AA

C4 - Haem and Glucose

C6 - FA

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9
Q

Explain metabolism in terms of breaking bonds.

A

Breaking C-C bonds forming CO2

Breaking C-H bonds and storing in NAD and FAD

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10
Q

Where does most of the energy in catabolism come from?

A

NADH and FADH2 transferring electrons to O2, releasing large amounts of energy for ATP synthesis

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11
Q

When intermediates are removed from TCA for biosynthesis, what replaces them?

A
  • Breakdown of other molecules, e.g AA
  • Pyruvate Carboxylase
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12
Q

How many molecules of ATP are produced from each glucose and how many from each FADH2 and NADH?

A
  • 32
  • 2.5 NADH
  • 1.5 FADH2

Energy released oxidation of these molecules used for oxidatitive phosphorylation

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13
Q

Explain the electron transport chain up to just before ATP synthase

A
  • 3 PTC
  • NADH oxidised. 2 electrons pass to PTC and energy from this used to transport 2H+ across membrane.
  • FADH oxidised at 2nd PTC
  • Electrons passed to each PTC and energy used to move H+.
  • Generates a proton motive force (electrochemical gradient)
  • Oxygen is terminal electron acceptor and combines with 2 electrons and 2 H+ to form water
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14
Q

How much of the energy from electrons is used to move H+ and what happens to the rest?

A

30%, rest of energy is lost as heat.

Tighter coupling, less energy loss to heat

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15
Q

Explain how ATP is synthesis via oxidative phosphorylation?

A
  • Oxidation of NADH set up p.m.f
  • Protons move down their gradient via ATP synthase
  • Energy from this dissapation is used to phosphorylate ADP
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16
Q

How is oxidative phosphorylation regulated?

A
  • High ATP, low ADP so no substrate
  • Inward flow of H+ down ATP synthase stops
  • Increase in H+ conc in intermembranal space
  • Stops further H+ pumping and electron transport
17
Q

How is oxidative phosphorylation affected?

A
  • Inhibitors (inhibition of electron transport, LETHAL, CN CO2)
  • Uncoupling (FA and dinitrophenol+crestol) (no inhibition of electron transport)

- ATP concentration

- Genetic defects in proteins (decrease electron transport)

18
Q

How do inhibitors stop oxidative phosphorylation?

A

e.g CN

Block electron transport by binding to PTC, preventing oxygen binding so electrons can’t be terminally accepted

No p.m.f

19
Q

How does uncoupling affect oxidative phosphorylation?

A
  • Uncouplers increase inner membrane permeability to H+
  • Protons can diffuse down gradient wihout ATP synthase, removing p.m.f
  • No p.m.f, no ATP synthesis, more energy lost to heat so get a temperature
  • Uses up fat for fuel as metabolism is uncontrolled when uncoupled as no ATP high energy signals
20
Q

How does brown adipose tissue release heat?

A
  • Contain thermogenin (UCP1)
  • Noradrenaline released when cold
  • Lipase stimuated, to release FA from TAG’s
  • FA oxidised, producing NADH for electron transport
  • Noradrenaloine activates UPC1
  • UPC1 transport H+ back into mitochondria, energy from p.m.f not used for ATP synthesis so dissapates it as heat
21
Q

Who has brown fat?

A

Babies, mainly around their vital organs

22
Q

Compare oxidative and substrate level phosphorylation.

A

Oxidative has more efficient energy conversion so less energy lost to heat.

Substrate uses phosphorylate compound, not Pi

23
Q

What is the summary of ATP synthesis from glucose?

A
24
Q

What are the key points of electron transport and ATP synthesis?

A
  • NADH and FADH2 reoxidised and energy released from electrons as transfer down PTC
  • O2 required
  • Large amounts of ATP produced
25
Q

What is dinitophenol and dinitrocresol and how do you treat them?

A
  • Uncouples, found in slimming pills and herbicides
  • Immediate referral to avoid death, e.g physical cooling, intravenous antioxidants like glutathione
26
Q

Describe all the stages of the Krebs Cycle.

A
27
Q

What are the functions of the TCA cycle?

A

Catabolic

  • Oxidise acetyl of acetyl coA to 2 CO2, GTP, NADH and FADH2
  • NADH and FADH2 oxidised in electron transport chain to generate ATP by phosphorylation

Anabolic

- Provide intermediates for synthesis of haem, glutamate, aspartate etc

  • Converting glucogenic amino-acids to glucose
28
Q

What are the consequences of a complete loss of enzyme in TCA cycle due to genetics?

A
  • Baby would not survive
  • Would make cycle inoperative so CNS and heart could not obtain enough energy to sustain life
29
Q

What are the key features of the electron transport chain?

A
  • Electrons are transferred from NADH (and FAD2H) through a series of TPC to molecular oxygen with the release of free energy.
  • The free energy is used to move protons from the inside to the outside of the inner mitochondrial membrane. The membrane itself is impermeable to protons and as electron transport proceeds the proton concentration on the outside of the inner membrane increases
30
Q

Why is cyanide toxic to our cells?

A

Binds to cytochrome site, stopping NADH and FADH being oxidised. Prevents generation of p.m.f and therefore ATP synthesis. No ATP then cell functions are impaired so cell death

31
Q

Bill, an agricultural worker, was employed by a farmer in East Anglia to spray 400 acres of wheat with a pesticide containing an aromatic weak acid, dinitrocresol (DNC). He failed to wear any protective clothing. After several days work, Bill fell ill with a very high temperature and profuse sweating. He was admitted to hospital, but in spite of strenuous attempts to decrease his body temperature, he fell into a coma and died. Autopsy showed a striking absence of subcutaneous fat.

Explain the symptoms.

A

Aromatic weak acids like 2-DNC (and 2,4-DNP) readily penetrate the mitochondrial inner membrane and act as uncoupling agents, i.e. they collapse the proton motive force and hence cause uncontrolled respiration to occur. This consumes large amounts of metabolic fuels (particularly fatty acids which are derived from fats stored in adipose tissue - hence the absence of subcutaneous fat) and of oxygen (this would lead to hypoxia but is prevented by increased pulmonary activity). As much less ATP than normal is made by oxidative phosphorylation under these conditions, a considerable amount of energy is lost as heat and the body temperature rises. When attempts to combat this by increased sweating eventually fail, the patient falls into a coma and dies.

32
Q
A