TCA cycle

Question 1

Why is the TCA cycle so relevant

Answer 1

• it is like the heart of metabolism
• it is the integration point of metabolic pathway
• it id the part of the complex process that turns food into energy
• no the TCA cycle there is no ATP , there is no life
• supplies energy in the form of electro carriers for the synthesis of ATP
• provides intermediates for the synthesis of AA, glucose, heme, nucleic acids etc

Question 2

The mitochondria has membranes

Answer 2

Mitochondrial matrix “impermeable” - TCA cycle

outer mitochondrial membrane “semi-permeable”

Inner mitochondrial membrane - ETC/oxidative phosphorylation

Question 3

How is pyruvate transferred across the impermeable mitochondrial membrane

Answer 3

MPC - mitochondrial pyruvate carrier

Question 4

Why are cofactors important in metabolism

Answer 4

they all require vitamins for their regeneration

Question 5

Are NAD and Coenzyme A electrons tightly bound or not?

Why?

Answer 5

not

Bc they are coenzymes and coenzymes are not tightly bound

Question 6

Are FAD electros tightly bound or not? Why?

Answer 6

they are tightly bound

Bc it is a prosthetic group and prosthetic groups are tightly bound

Question 7

Where is CoA needed in the TCA cycle?

slide 11

Answer 7

1st biochemical rxn - acetyl CoA –> citrate by citrate synthase (hydrolysis)

5th biochemical rxn - succinyl CoA –> succinate, substrate level phosphorylation

Question 8

Why is niacin (vit b3) important?

Answer 8

For the generation of NAD+

Question 9

What is the rate limiting step in TCA cycle?

Answer 9

• 3rd biochemical rxn,
• oxidative decarboxylation of isocitrate (going from 6C to 5C)
• Electrons are also lost, but NAD picks them up (2e- 1H)

Question 10

Where do you see FAD in TCA?

Answer 10

6th biochemical rxn

Question 11

What is one important key control in the TCA cycle?

Answer 11

4th biochemical reaction
oxidative decarboxylation of a-ketoglutarate –> succinyl CoA

Driven by a-ketoglutarate dehydrogenase. It’s a complex with:
5 coenzymes
3 enzymes
4 vitamins

If body is deficient in any of the vitamins, this affects how TCA cycle works

Question 12

Is the overall energetics of the TCA cycle favourable?

Answer 12

Yes. it is exergonic so the forward direction would be favored

Question 13

What are the precursors of acetyl CoA?

Answer 13

fatty acid
ketone bodies 
sugar 
pyruvate,
ethanol

Question 14

What plays an anabolic role of Citric acid cycle?**

Answer 14

PEP, Oxaloacetate

Question 15

Which is the cofactor for pyruvate carboxylase?

Answer 15

Biotin - has a prosthetic group

Question 16

What are the role of vitamins in TCA?
riboflavin
niacin
thiamin
pantothenic acid

Answer 16

riboflavin - regenerating FAD

niacin - generating NAD+

Thiamin - coenzyme for decarboxylation of a-ketoglutarate dehydrogenase reaction

Pantothenic acid - coenzyme A

Question 17

What can impair the function of TCA>

Answer 17

• impaired oxidation of pyruvate –> leads to buildup of lactate
• Lack of O2 - impairs TCA cycle function (important in ETC and oxidative phosphorylation?

Question 18

The principal function of the TCA cycle is to:

1. Generate CO2
2. Dispose of excess pyruvate and fatty acids.
3. Generate ATP from AA
4. Transfer elections from acetyl portion of acetyl CoA to NAD+ and FAD

Answer 18

4. Transfer elections from acetyl portion of acetyl CoA to NAD+ and FAD

Question 19

A patient diagnosed with thiamine deficiency exhibited fatigue and muscle cramps. The muscle cramps have been related to an accumulation of which of the following metabolic acids?

1. succinic acid
2. fumaric acid
3. malic acid
4. Isocitric acid

Answer 19

4. Isocitric acid

Thiamin= coenzyme for decarboxylation of a-ketoglutarate dehydrogenase reaction therefore, if the reaction stops there, accumulation occurs the step before it.

Question 20

What is the fuel of the TCA cycle?

Answer 20

Acetyl CoA

Question 21

For diagrams. check slides:

Answer 21

4
6
7
9
18
20
21 - oxaloacetate & PEP
23 anaplerotic rxns

Question 22

Key features of the TCA cycle

Answer 22

Is an oxidative pathway

central hub of metabolism for energy production and biosynthesis

8 biochemical reactions (catalyzed by different enzymes)

4 Oxidation/reduction steps to extract high energy electrons

O2 is not required but participates indirectly

Question 23

What are the products of the TCA cycle per turn?

Answer 23

1 ATP
3 NADH
1 FADH2
2 CO2

Question 24

List the cofactors in energy metabolism with their vitamin and what they carry

Answer 24

1. NAD+:
   coenzyme
   niacin
   e-
2. FAD
   prosthetic group
   riboflavin
   e-
3. Coenzyme A
   coenzyme
   pantothenic group
   acyl group

Question 25

Importance of Coenzyme A

Answer 25

precursor of acetyl coA (along with acetyl ​group from pyruvate)

• activation transfer co-factor
• transfers 2 C acyl units )eg acetyl)
• hydrolysis of the thioester bond (high energy bond) is exergonic
• reversible binding to enzyme

Question 26

How does NAD+ work?

Answer 26

It picks up some electrons and H to change between oxidized and reduced forms

Question 27

How does FAD work?

Answer 27

Oxidized FAD accepts 2 electrons & 2 H+ to form reduced FADH2

Has a role in both TCA and ETC

Question 28

What are some additional coenzymes in the TCA?

Answer 28

Thiamine

Lipoamide (electron/acyl carrier)

Question 29

Is the TCA cycle catabolic, anabolic or amphibolic?

Answer 29

Amphibolic

Question 30

What are anaplerotic reactions?

Answer 30

• maintain the concentrations of TCA cycle intermediates constant (cell is always able to provide the intermediates)
  eg: if oxaloacetate is low, pyruvate can be redirected to help make more

Allows TCA cycle to function during periods of active biosynthesis