Koc - Citric Acid Cycle

Question 1

Citric Acid Cycle Stages

Answer 1

Acetyl-CoA Production

Acetyl-CoA Oxidation

Electron Transfer and Oxidative Phosphorylation

Question 2

What is the source of majority of ATP (energy) production?

Answer 2

Complete oxidation of pyruvate in mitochondria

Question 3

Fate of Pyruvate: Anaerobic Condition

Answer 3

Lactate (LDH)

Question 4

Fate of Pyruvate: Amino Acid Synthesis?

Answer 4

Alanine

Question 5

Fate of Pyruvate: Aerobic Conditions

Answer 5

Acetyl-CoA (PDH complex driven)

Enters Citric Acid Cycle fo further oxidation

Question 6

Fate of Pyruvate: Anaplerotic Reaction / Gluconeogenesis

Answer 6

Oxaloacetate (Pyruvate Carboxylase)

Replenish citric acid cycle intermediates

Question 7

What is Acetyl-CoA oxidized to in the Citric Acid Cycle?

Answer 7

CO₂

Question 8

How is Pyruvate converted to Acetyl-CoA?

Answer 8

Oxidative Decarboxylation through Pyruvate Dehydrogenase Complex

Question 9

What does the oxidative decarboxylation of Pyruvate to Acetyl-CoA require?

Answer 9

3 enzymes, 5 coenzymes

TPP, Lipoyllysine, FAD proesthetic groups

NAD+, CoA-SH co-substrates

Question 10

What are three enzymes of PDH?

Answer 10

E1: Pyruvate Dehydrogenase

E2: Dihydrolipoyl Transacetylase

E3: Dihydrolipoyl Dehydrogenase

Question 11

TPP Deficiency

Answer 11

Thiamin - B1

Beriberi / Wenicke-Korsakoff

Question 12

NAD+ Deficiency

Answer 12

Niacin - B3

Pellagra (skin, psycho)

Question 13

FAD Deficiency

Answer 13

Riboflavin - B2

Cheilosis

Question 14

How is the Pyruvate Dehydrogenase complex regulated?

Answer 14

Phosphorylated = Inactive

Dephosphorylated = Active

Activate Phosphatase: Mg²⁺, Ca²⁺

Inhibit Kinase: Insulin, Pyruvate, NAD, CoA

(same result)

Inhibit Enzyme: NADH, Acetyl-CoA (end products)

Activate Kinase: Glucocorticoids, Insulin, Growth/thyroid hormones, Tyrosine kinase

Question 15

What induces the Warburg Effect in cancer cells?

Answer 15

OXPHOS is inhibited due to highly active:

Pyruvate Dehydrogenase Kinase I, III

(inactivates PDH)

Question 16

What is the final oxidative pathway in catabo;ism of carbs, amino acids, and fatty acids?

Answer 16

Citric Acid Cycle

Question 17

What is net (per Acetyl CoA) in each turn of Citric Acid Cycle?

Answer 17

3 NADH

1 FADH₂

1 GTP

Question 18

How many ATP does the complete oxidation of one mole glucose produce?

Answer 18

30-32 ATP

Question 19

What is first step of citric acid cycle?

Answer 19

2-C acetyl coa + 4-C OAA = 6-C citrate

Question 20

What are the main intermediates in the Citric Acid Cycle?

Answer 20

1. Oxaloacetate + Acetyl CoA = Citrate
2. Citrate -> a-Ketoglutarate
3. a-Ketoglutarate -> Succinyl CoA
4. Succinyl CoA -> Fumarate
5. Fumarate -> OAA

Question 21

CAC: Reation 1: Citrate Synthase

Answer 21

Acetyl-CoA + OAA = Citrate

Enzyme: Citrate Synthase

Only reaction with C-C bond formation

RATE LIMITING STEP

Activity depends on [OAA]

High [OAA] drives forwards, favorable/irreversible

Question 22

CAC: Reation 2: Aconitase

Answer 22

Citrate -(aconitase)- cis-Aconitase -(aconitase)- Isocitrate

Enzyme: Aconitase (isomerization rxn)

Unavorable/Reversible

Low [Product] pulls forward

Requires H₂O

Question 23

CAC: Reation 3: Isocitrate Dehydrogenase

Answer 23

Isocitrate -(isocitrate dehydrogenase)- {decarboxylation} - a-Ketoglutarate

Enzyme: Isocitrate Dehydrogenase

LOSE: CO₂

GAIN: NADH

- - -

Favorable/Irreversible

Regulated by product inhibition, ATP

Question 24

CAC: Reation 4: a-Ketoglutarate Dehydrogenase

Answer 24

a-Ketoglutarate -(a-Ketoglutarate dehydrogenase complex)- Succinyl-CoA

5-Carbon to 4-Carbon

Enzyme: a-Ketoglutarate Dehydrogenase

Produce: CO₂

Produce: NADH

- - -

Net full oxidation of all carbons of glucose

Carbons lost come from OAA

Needs same 5 coenzymes as PDH complex

Regulated by product inhibition

Favorable/irreversible

Question 25

CAC: Reation 4: a-Ketoglutarate Dehydrogenase is highly dependent on what?

Answer 25

Vitamin cofactors/coenzymes

Question 26

Where do lost carbon atoms come from in the Citric Acid Cycle?

Answer 26

Oxaloacetate (OAA)

Question 27

CAC: Reation 5: Succinyl-CoA Synthetase

Answer 27

Succinyl-CoA -(succinyl CoA synthetase)- Succinate

Requires energy

Substrate level phosphorylation

- - -

Produces GTP (makes ATP)

Low [Succinate] pulls forward

Question 28

CAC: Reation 6: Succinate Dehydrogenase

Answer 28

Succinate -(Succinate Dehydrogenase)- Fumarate

Only membrane bound enzyme

- - -

Requires: FAD

Produces: FADH₂

Reversible

[Product] pulls forward

Question 29

CAC: Reation 7: Fumarase

Answer 29

Fumarate -(fumarase)- Malate

[Product] pulls forward

Question 30

CAC: Reation 8: Malate Dehydrogenase

Answer 30

Malate -(malate dehydrogenase)- OAA

Oxidation of alcohol to ketone

Final Step

- - -

Require: NAD+

Produces: NADH

Highly UNFAVORABLE/reversible

Question 31

What keeps [OAA] low in citric acid cycle?

Answer 31

Citrate Synthase

Question 32

What is net of CAC per acetyl-coa?

Answer 32

2 CO₂

3 NADH

1 FADH₂

1 GTP

Question 33

What anaplerotic reactions occur to provide CAC w/intermediates?

Answer 33

Pyruvate to OAA (Pyruvate Carboxylase)

Pyruvate to Malate (Malic Enzyme)

PEP to OAA (PEP Carboxykinase)

Question 34

What type of amino acids can generate 3, 4, 5C intermediates of CAC?

Answer 34

Glucogenic

Question 35

What enzymes are regulated in the CAC?

How are they regulated?

Answer 35

PDH Complex

Citrate Synthase

Isocitrate Dehydrogenase

a-Ketoglutarate Dehydrogenase Complex

ACTIVATE: Low Energy (AMP, CoA, NAD+, Ca2+)

INHIBIT: High Energy (ATP, NADH, Fatty Acids)

INHIBIT: End products (Citrate, succinyl-CoA)

Question 36

High ATP/ADP , NADH/NAD+, Acetyl-CoA/CoA ratio effect on CaC?

Answer 36

Inhibits