TCA Cycle

Question 1

What is the TCA Cycle also known as?

Answer 1

• Krebs Cycle]
• Citric Acid Cycle

Question 2

Where does the TCA Cycle occur?

Answer 2

Mitochondrial Matrix

Question 3

What type of metabolic pathway is the TCA Cycle?

Answer 3

TCA Cycle is Amphibolic, it possesses Anabolic + Catabolic properties.

Question 4

Define Catabolic and Anabolic in the context of the TCA Cycle.

Answer 4

Anabolic: Building biomolecules from TCA intermediates (e.g., oxaloacetate → glucose)

Catabolic: Breakdown of Acetyl-CoA to generate energy (ATP, NADH, FADH₂)

Question 5

How is the TCA Cycle Catabolic?

Answer 5

Fully oxidizes acetyl-CoA → releases CO₂

Produces: 3 NADH, 1 FADH₂, 1 GTP per turn (→ ATP via ETC).

Question 6

How is the TCA Cycle Anabolic?

Answer 6

Because TCA Intermediates exit to biosynthesize:

Oxaloacetate → glucose (gluconeogenesis) or aspartate.

α-Ketoglutarate → glutamate (→ other amino acids, purines).

Succinyl-CoA → heme (for hemoglobin).

Citrate → fatty acids/cholesterol.”

Question 7

What is the link from Glycolysis to the TCA Cycle?

Answer 7

Pyruvate Dehydrogenase (PDH), which converts pyruvate (from glycolysis) into Acetyl-CoA, allowing it to feed into the TCA Cycle.

Without PDH, pyruvate cannot be fed into TCA Cycle

Question 8

What are the preparatory steps of the TCA Cycle?

Answer 8

Pyruvate transported into mitochondrial matrix using pyruvate translocase

Pyruvate Dehydrogenase converts pyruvate into Acetyl-CoA

Done By:
Pyruvate + CoA + NAD⁺ → Acetyl-CoA + NADH + CO₂

Question 9

How many Stages of the TCA Cycle are there?

Answer 9

8

Question 10

What is Stage 1 of the TCA Cycle?

Answer 10

Citrate Synthase catalyzes reaction between Acetyl-CoA and Oxaloacetate, leading to formation of Citrate#

Acetyl-CoA + Oxaloacetate (OAA) → Citrate

Condensation reaction

Question 11

What is Stage 2 of the TCA Cycle?

Answer 11

Aconitase converts Citrate into Isocitrate via a re-arrangement reaction with cis-aconitate intermediate

Isomerization

Question 12

What Stage 3 of the TCA Cycle?

Answer 12

Isocitrate dehydrogenase converts isocitrate into α-Ketoglutarate

Products:
α-Ketoglutarate
NADH
CO₂

Oxidative Decarboxylation

Question 13

What is Stage 4 of the TCA Cycle?

Answer 13

α-Ketoglutarate dehydrogenase complex converts α-Ketoglutarate into Succinyl-CoA

Oxidative Decarboxylation

Question 14

What is Stage 5 of the TCA Cycle?

Answer 14

Succinyl-CoA synthetase converts Succinyl-CoA into succinate.

GTP produced at substrate level phosphorylation

Substrate-level phosphorylation

Question 15

What is Stage 6 of the TCA Cycle?

Answer 15

Succinate dehydrogenase converts Succinate into Fumarate + FADH₂

Oxidation

Question 16

What is Stage 7 of the TCA Cycle?

Answer 16

Fumarate is hydrated, leads to the formation of Malate

Hydration

Question 17

What is Stage 8 of the TCA Cycle?

Answer 17

Malate Dehydrogenase converts Malate to Oxaloacetate

NADH produced, regenerates Oxaloacetate to restart cycle

Oxidation

Question 18

What products form every time Acetyl-CoA enters the TCA Cycle?

Answer 18

3 NADH In Stage 3,4,8
1 FADH₂ In Stage 6
1 GTP In Stage 5
2 CO₂ Release (Isocitrate + α-Ketoglutarate dehydrogenase)

Question 19

What Happens In Starvation?

Answer 19

Body runs out of glucose/glycogen, has to burn fats

Muscle Wasting:

1. Muscle protein broken down to generate Glucogenic Amino Acids (GAA)
2. GAA transported to liver, converted into glucose by gluconeogenesis

Question 20

Why can’t Fatty Acids be converted into glucose?

Answer 20

Pyruvate dehydrogenase is irreversible
Fatty acids cannot cross brain barrier

Question 21

Which intermediate in the TCA cycle do amino acids NOT feed into?

Answer 21

Answer: Isocitrate

Reason:
Oxaloacetate (c): Amino acids like aspartate/asparagine feed into oxaloacetate.

Fumarate (a): Amino acids e.g. phenylalanine/tyrosine (via tyrosine degradation) feed into fumarate.

α-Ketoglutarate: Glutamate/glutamine feed into α-ketoglutarate.

Succinyl-CoA: Methionine, valine, and isoleucine feed into succinyl-CoA.

Isocitrate (b) is not direct product of amino acid metabolism. It is formed enzymatically from citrate via aconitase in the TCA cycle itself

Question 22

How Do Fatty Acids Feed Into the TCA Cycle?

Answer 22

Via acetyl CoA and succinyl CoA

Explanation:

Fatty acids feed into TCA cycle through 2 pathways depending on structure:

Most fatty acids (even-chain): Undergo β-oxidation, breaking down into acetyl-CoA

Acetyl-CoA enters TCA cycle by combining with oxaloacetate to form citrate (the first step of the cycle).

Odd-chain fatty acids (less common):

β-oxidation produces 1 molecule of propionyl-CoA (3-carbon unit) in final step

Propionyl-CoA converted to succinyl-CoA ( TCA intermediate) via:

Propionyl-CoA → methyl malonyl-CoA → succinyl-CoA.

Succinyl-CoA directly enters the TCA cycle.