Metabolism 4

Question 1

What makes acetyl-CoA so useful?

Answer 1

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

Question 2

Briefly describe what happens in the TCA/Krebs cycle.

OCI ASS FMO

Answer 2

-8 reactions

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

Question 3

Reaction 1 of TCA

Answer 3

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

(Acetyl-CoA ——> HS-CoA + H+)

Enzyme: citrate synthase

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

Question 4

Reaction 2 of TCA

Answer 4

2. Citrate ——–> Isocitrate

Enzyme: Aconitase

Question 5

Reaction 3 of TCA

Answer 5

3. Isocitrate ———> a-ketoglutarate6C ———————–> 5C

NAD+ ——> NADH + CO2 + H+

Enzymes: Isocitrate dehydrogenase

Isocitrate is oxidised

Question 6

Reaction 4 of TCA

Answer 6

4. a-ketoglutarate ———-> succinyl-CoA

     5C  ---------------------------> 4C

NAD+ —-> NADH + CO2 + H+

Enzyme: a-ketoglutarate dehydrogenase complex

Question 7

Reaction 5 of TCA

Answer 7

5. Succinyl-CoA ———> Succinate

     H20------------> HS-CoA
   
      GDP + Pi ---------> GTP

Enzyme: succinyl-CoA synthetase

Question 8

Whats special about GTP?

Answer 8

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

Question 9

Reaction 6 of TCA

Answer 9

6. Succinate ————> Fumarate

   FAD -------------------------> FADH2

Enzyme: Succinate dehydrogenase

Question 10

Reaction 7 of TCA

Answer 10

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

Enzyme: Fumerase

Question 11

Reaction 8 of TCA

Answer 11

8. Malate ——————–> OxaloacetateNAD+ ——————————> NADH + H+

Enzyme: Malate dehydrogenase

Question 12

What does one overall turn through the TCA cycle produce?

Answer 12

1. 3xNADH
2. 1xGTP
3. 1xFADH2
4. 2xCO2

Question 13

Where are the Krebs cycle enzymes located?

EXCEPT SUCCINATE DEHYDROGENASE

Answer 13

Soluble proteins in the MITOCHONDRIAL MATRIX

Question 14

Where is succinate dehydrogenase located?

Answer 14

Firmly attached to inner surface of inner mitochondrial membrane.

It is an integral membrane protein.

Question 15

How come Krebs cycle only operates under aerobic conditions?

Answer 15

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

Question 16

How many ATPs can a NADH generate?

Answer 16

3

Question 17

How many ATPs can a FADH2 generate?

Answer 17

2

Question 18

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

Answer 18

12

Question 19

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

Answer 19

Glycolysis = 8 ATP (2ATP + 2NADH)

Link = 6 ATP (2 NADH)

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

=38 ATP

Question 20

How are AAs degraded?

Answer 20

1. AA group removed (excreted as urea)

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

Question 21

Which 7 molecules can all AAs be degraded to

Answer 21

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

Question 22

Protein metabolism involves transamination reactions. What are transamination reactions?

Answer 22

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

This forms a new pair of AA and keto acid

Question 23

Describe the protein metabolism of Alanine.

Answer 23

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

Question 24

How does NADH from the cytosol enter the mitochondrial matrix?

Answer 24

1. Through the Glycerol Phosphate shuttle

2. Through the Malate-Aspartate shuttle

Question 25

Where is the Glycerol Phosphate shuttle located?

Answer 25

Skeletal muscle, brain

Question 26

Where is the Malate Aspartate shuttle located?

Answer 26

Liver, kidney, heart

Question 27

Explain the Glycerol Phosphate shuttle.

Answer 27

(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.

Question 28

Explain the Malate Aspartate shuttle.

Answer 28

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).

Question 29

What is the transporter for malate?

Answer 29

a-ketoglutarate

Question 30

What is the transporter for aspartate?

Answer 30

glutamate/aspartate transporter

Question 31

How are the transporters able to cycle molecules around?

Answer 31

Transamination reactions. Glutamate + oxaloacetate --------> a-ketoglutarate + aspartate

Question 32

Which co factor is anabolic?

Answer 32

NADPH is anabolic

Question 33

Which co factor is catabolic?

Answer 33

NADH is catabolic

Question 34

Compare and contrast NADP+ and NAD+.

Answer 34

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+

Question 35

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

Answer 35

It is held in a high energy linkage.