Metabolism 4 Flashcards

1
Q

What makes acetyl-CoA so useful?

A

Its thioester bond is a high energy linkage which is readily hydrolysed - allows Acetyl-CoA to donate acetate (2C) to other molecules

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2
Q

Briefly describe what happens in the TCA/Krebs cycle.

OCI ASS FMO

A

-8 reactions

  • starts with 2C atoms from Acetyl-CoA
  • 2C combined with 4C oxaloacetate to give a 6C unit, citrate
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3
Q

Reaction 1 of TCA

A
  1. Oxaloacetate ——–> citrate4C ——————–> 6C

(Acetyl-CoA ——> HS-CoA + H+)

Enzyme: citrate synthase

2C acetyl group transferred to 4C oxaloacetate forming 6C citrate.

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4
Q

Reaction 2 of TCA

A
  1. Citrate ——–> Isocitrate

Enzyme: Aconitase

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5
Q

Reaction 3 of TCA

A
  1. Isocitrate ———> a-ketoglutarate6C ———————–> 5C

NAD+ ——> NADH + CO2 + H+

Enzymes: Isocitrate dehydrogenase

Isocitrate is oxidised

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6
Q

Reaction 4 of TCA

A
  1. a-ketoglutarate ———-> succinyl-CoA
      5C  ---------------------------> 4C

NAD+ —-> NADH + CO2 + H+

Enzyme: a-ketoglutarate dehydrogenase complex

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7
Q

Reaction 5 of TCA

A
  1. Succinyl-CoA ———> Succinate
      H20------------> HS-CoA
    
       GDP + Pi ---------> GTP

Enzyme: succinyl-CoA synthetase

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8
Q

Whats special about GTP?

A

It can be used to catalyse ATP formation from ADP in the presence of a nucleoside diphosphokinase

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9
Q

Reaction 6 of TCA

A
  1. Succinate ————> Fumarate
    FAD -------------------------> FADH2

Enzyme: Succinate dehydrogenase

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10
Q

Reaction 7 of TCA

A
  1. Fumarate —————–> MalateH20 INSERTED (to break double bond)

Enzyme: Fumerase

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11
Q

Reaction 8 of TCA

A
  1. Malate ——————–> OxaloacetateNAD+ ——————————> NADH + H+

Enzyme: Malate dehydrogenase

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12
Q

What does one overall turn through the TCA cycle produce?

A
  1. 3xNADH
  2. 1xGTP
  3. 1xFADH2
  4. 2xCO2
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13
Q

Where are the Krebs cycle enzymes located?

EXCEPT SUCCINATE DEHYDROGENASE

A

Soluble proteins in the MITOCHONDRIAL MATRIX

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14
Q

Where is succinate dehydrogenase located?

A

Firmly attached to inner surface of inner mitochondrial membrane.

It is an integral membrane protein.

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15
Q

How come Krebs cycle only operates under aerobic conditions?

A

Because NAD+ and FAD+ are only regenerated in oxidative phosphorylation when e- are transferred to O2.

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16
Q

How many ATPs can a NADH generate?

A

3

17
Q

How many ATPs can a FADH2 generate?

A

2

18
Q

How many ATPs will the oxidation of 1 Acetyl-CoA give?

A

12

19
Q

From 1 glucose molecule, how much ATP can be derived.

A

Glycolysis = 8 ATP (2ATP + 2NADH)

Link = 6 ATP (2 NADH)

TCA = 24 ATP (6 NADH, 2 FADH2, 2 GTP)

=38 ATP

20
Q

How are AAs degraded?

A
  1. AA group removed (excreted as urea)

2. C skeleton used for glucose production or fed into TCA cycle

21
Q

Which 7 molecules can all AAs be degraded to

A
  1. Pyruvate
  2. Acetyl CoA
  3. Acetoacetyl CoA
  4. a-ketoglutarate
  5. Succinyl CoA
  6. Fumarate
  7. Oxaloacetate
22
Q

Protein metabolism involves transamination reactions. What are transamination reactions?

A

Reaction where an amine group is transferred from an AA to a keto acid.

This forms a new pair of AA and keto acid

23
Q

Describe the protein metabolism of Alanine.

A
  1. Alanine transaminated by Alanine aminotransferase
  2. Alanine + a-ketoglutarate —–> Pyruvate + glutamate
  3. Pyruvate can enter TCA cycle
  4. Glutamate converted back to a-ketoglutarate. Generates NH4+ which is excreted as urea.
  5. Loads of alanine aminotransferase may signal hepatic disorders
24
Q

How does NADH from the cytosol enter the mitochondrial matrix?

A
  1. Through the Glycerol Phosphate shuttle

2. Through the Malate-Aspartate shuttle

25
Q

Where is the Glycerol Phosphate shuttle located?

A

Skeletal muscle, brain

26
Q

Where is the Malate Aspartate shuttle located?

A

Liver, kidney, heart

27
Q

Explain the Glycerol Phosphate shuttle.

A

(1. e- from NADH (not the NADH itself), are carried across the mitochondrial membrane.)
2. Cytosolic G3P dehydrogenase transfers e- from NADH to G3P
3. Membrane bound G3P dehydrogenase (aka mitochondrial G3P dehydrogenase) transfers these e- to FAD.
4. From FAD, the e- get passed to coenzyme Q, which is part of the e- transport chain.

28
Q

Explain the Malate Aspartate shuttle.

A

Overall, this is the reaction that occurs:

NADH (cytoplasmic) + NAD+ (mitochondrial) ————> NAD+ (cytoplasmic) + NADH (mitochondrial)

  1. H- ion transferred from cytoplasmic NADH to oxaloacetate to give malate (catalysed by cytosolic malate dehydrogenase).
  2. Malate transported into mitochondria where its rapidly deoxidised by NAD+ to give oxaloacetate and NADH (catalysed by mitochondrial MDH).
29
Q

What is the transporter for malate?

A

a-ketoglutarate

30
Q

What is the transporter for aspartate?

A

glutamate/aspartate transporter

31
Q

How are the transporters able to cycle molecules around?

A

Transamination reactions.

Glutamate + oxaloacetate ——–> a-ketoglutarate + aspartate

32
Q

Which co factor is anabolic?

A

NADPH is anabolic

33
Q

Which co factor is catabolic?

A

NADH is catabolic

34
Q

Compare and contrast NADP+ and NAD+.

A

Both can pick up a hydride ion.

Both are e- carriers.

NADP+ is similar to NAD+ except it differs as it has a phosphate group attached to a ribose ring.

Phosphate present on NADP+ means it binds to different enzymes than NAD+

35
Q

How come the H- ions easily transferred to other molecules?

A

It is held in a high energy linkage.