CAC

Question 1

In the CAC, the acetyl molecule is ultimately oxidized to what?

Answer 1

CO2

Question 2

What amount of the total ATP produced in the body is made in CAC

Answer 2

2/3

Also most of the CO2 we exhale is from the CAC

Question 3

Which reaction #s are oxidation/reduction reactions?

Answer 3

3, 4, 6, 8

3,4 = oxidative decarboxylation (CO2 is removed)

Question 4

Which reaction is a substrate-level phosphorylation reaction

Answer 4

5

Producing GTP

Question 5

The CO2 produced in the CAC come originate from what molecule?

Answer 5

OAA (not Ac-CoA)

2 total

Question 6

Citrate synthase

Answer 6

Ac-CoA is condense with OAA —> citrate

CoA group is removed…hydrolysis of thioester bond between carbon and sulfur group

Irreversible

Inhibited by product feedback (citrate)

Recall: citrate also inhibitor of glycolytic PFK-1 enzyme

Question 7

Aconitase

Answer 7

Citrate —> isocitrate

Isomerization of C-3 OH group —> C-5 position

Reversible

Cis-aconitate = intermediate

1st step = dehydration
2nd step = hydration

Question 8

Isocitrate dehydrogenase

Answer 8

Isocitrate —> alpha-ketoglutarate

Makes CO2 and NADH

Irreversible

Question 9

Alpha-KG dehydrogenase complex

Answer 9

A-KG —> succinyl-CoA

Makes NADH and CO2

Mechanically similar to PDH complex
—> needs SAME vitamin cofactors!

Irreversible

Question 10

Succinyl-CoA synthetase

Answer 10

Substrate-level phosphorylation

Succinyl-CoA —> succinate

1. Breaks thioester bond in succinyl-CoA
   —> succinyl phosphate intermediate
2. Phosphate group is transferred to the enzyme —> liberating succinate
3. High energy phosphate group is transferred to GDP —> GTP

Irreversible

Question 11

Succinate dehydrogenase

Answer 11

Succinate —> Fumarate

Makes FADH2

This enzyme is associated with the inner membrane of the mitochondria

Therefore, the electrons can be fed directly into the e-transport chain

Reversible

Question 12

Fumarase

Answer 12

Fumarate —> malate

Water is added across the double bond in fumarate to create a OH group in malate

Reversible

Question 13

Malate dehydrogenase

Answer 13

Malate —> OAA

Makes NADH

Reversible

Question 14

Yield of CAC

Answer 14

2 CO2

3 NADH = 3*2.5ATP = 7.5 ATP

FADH2 = 1.5 ATP = 1.5 ATP

GTP = 1 ATP

CoASH

TOTAL ATP = 10 ATP

Question 15

Overally efficiency of CAC

Answer 15

Total amount of energy is Acetyl group = ~228 kcal/mole

Energy produced in CAC ~~ 207 kcal/mol

90% efficiency

Question 16

Main type of CAC regulation

Answer 16

Allosteric regulation

Within mitochondria

Question 17

Effect of ADP

Answer 17

Low-energy state

Stimulates reactions 3 and 4

Question 18

Effect of NADH

Answer 18

As [NADH]&raquo_space;» [NAD+] —> high energy state

Reactions 3, 4, and 8 = inhibited since NAD+ = a cofactor

NADH = most inhibitory effect on the pathway

Question 19

Effect of Ca2++

Answer 19

Stimulates reactions 3 and 4

Same effect it did on the PDH complex

Much energy is used in muscle contraction and Ca2+ stores are released from the SER —> will stimulate CAC reaciton

Question 20

Citrate regulation

Answer 20

Feed back inhibition on its own synthesis

By citrate synthase

Question 21

Important CAC intermediates and what they are used for

Answer 21

1. Citrate —> FAS and sterol formation
2. A-KG —> converted to glutamate, which is used to make other aa and purine synthesis
3. OAA —> converted to asparate, which is used to make other aa and purine/pyrimidine syn.
4. Succinyl-CoA —> make porphyrins or heme

Question 22

How CAC intermediates are replenished

Answer 22

1. Pyruvate carboxylase rxn —> makes OAA from pyruvate
2. A-Kg produced from glutamate
3. Succinyl-CoA made from valine, isoleucine, or certin fatty acids
4. Fumarate can be made from certain aa
5. Asparate can replenish OAA also

Question 23

How do reduced electron equivalents get from cytosol —> mitochondria

Answer 23

Gylcerol phosphate shuttle —> makes 1.5 ATP per shuttle

Malate-asparate shuttle —> makes 2.5

Question 24

Glycerol phosphate shuttle

Answer 24

In the cytosol…glycerol 3-phosphate dehydrogenase oxidized NADH —> NAD+

At the same time…DHAP is reduced to glycerol-3P

At the IMM…G3P is reoxidized by membrane-bound G3P dehydrogenase back to DHAP

In matrix…those electrons reduce FAD —> FADH2