Citric Acid Cycle

Question 1

Location of citric acid cycle and why it is significant?

Answer 1

Mitochondrial matrix; cells with mitochondria will generate a bulk of ATP (TCA makes a lot of ATP)

Question 2

What is the gateway between TCA and glycolysis?

What does this do in TCA?

Answer 2

Pyruvate dehydrogenase complex (PDH)

Converts pyruvate to acetyl CoA

Question 3

** PDH complex is a regulatory point for metabolism

1. What does it produce?
2. What does it require in order to work?

Answer 3

1. NADH (1 per mol of pyruvate)
2. 5 vitamin B derived coenzymes: thiamine pyrophosphate (TPP), lipoamide, coenzyme A (CoA), FAD, and NAD+

~PDH complex needs all 5 of these to work

Question 4

Difference in structure between pyruvate and acetyl CoA?

Answer 4

Pyruvate is a 3 carbon molecule; acetyl CoA is a 2 carbon molecule

Question 5

Thiamin pyrophosphate (TPP)(vitamin B1 deficiency) is commonly seen in what kind of people?

Another name for TPP in alcoholics?

Is this reversible?

Answer 5

Chronic alcoholics (vitamin deficient because they usually do not eat a balanced diet)

Wernicke Korsakoff syndrome

It is reversible unless they progress to the stage of psychosis; then it is not reversible

Question 6

What is beri beri?

Describe the two types

Answer 6

Clinical presentation that you would get if you have TPP and you are not alcoholic

Wet type- cardiovascular presentations
Dry type- peripheral neuropathy

Question 7

Two clinical presentations resulting from Niacin (B3) deficiency?

From FAD (riboflavin) deficiency?

Answer 7

Pellagra and dermatitis

Ulcers (angular stomatitis, cheilosis, glossitis)

Question 8

1. Does PDH get activated in high energy state or low energy state?
2. What is it activated by?
3. Inhibited by?

Answer 8

1. Low energy state
2. Increased AMP and increased NAD+
3. Its products (increased Acetyl CoA and increased [NADH]/[NAD+] ratio

Question 9

What is the substrate and starting molecule for the TCA cycle

Answer 9

Acetyl CoA

Question 10

How does acetyl CoA enter TCA?

What catalyzes this?

What is significant about this step?

Answer 10

By reacting with oxaloacetate to form citrate

Citrate synthase

It is the first regulated step of the cycle

Question 11

First step where NADH is produced converts what to what?

Other thing significant about this step?

Answer 11

Isocitrate is converted to alpha ketoglutarate

Second regulated step of the cycle

Question 12

1. Which enzyme is structurally similar to PDH complex?

2. What is the third regulated step of the cycle? Hint: it is done by enzyme from 1.

Answer 12

1. Alpha ketoglutarate dehydrogenase complex

2. Alpha ketoglutarate to succinyl-CoA

Question 13

The next step produces GTP from synthesizing GDP and Pi. Why is this significant?

Answer 13

It forms the first substrate for phosphorylation (GTP enters the cycle again)

Question 14

Only enzyme that is present on the inner membrane of mitochondra (and complex II of ETC?

Oxidizes what to what?

Answer 14

Succinate dehydrogenase

FADH2 to FAD (by ETC)

Question 15

__ converts to ___ by what enzyme to generate NADH from NAD

Answer 15

L-malate converts to oxaloacetate by enzyme malate dehydrogenase

Question 16

What is something else besides low energy that activates TCA cycle?

Answer 16

Calcium; so when you are working out TCA is activated

Question 17

When PDH converts pyruvate to acetyl CoA, what does it generate?

Answer 17

1 NADH = 1 ATP

Question 18

Each mole of acetyl CoA enters TCA cycle generates:

Answer 18

3 NADH = 9 ATP
1 FADH2 = 2 ATP
1 GTP = 1 ATP

Total = 12 ATP

Question 19

Under aerobic conditions, how many ATP are generated by glycolysis and TCA?

Anaerobic?

Answer 19

33-38 ATP (depending on shuttles)

2 ATP (TCA not applicable in anaerobic)

Question 20

Fluoroacetate causes death by inhibition of?

Answer 20

Aconitase

Question 21

Glycolysis produces?

How do these high energy electrons get into the mitochondria in order to enter ETC?

Answer 21

2 NADH/molecule of glucose

NADH cannot permeate the membrane so need to use either malate-aspartate shuttle or glycerol-3-phosphate shuttle