TCA CYCLE

What is the citric acid cycle?

• An 8-step metabolic pathway that oxidizes acetyl-CoA.

• Produces CO₂ and reduced electron carriers used to generate ATP

What are the other names for the citric acid cycle?

• Krebs cycle.

• Tricarboxylic acid (TCA) cycle.

Where does the citric acid cycle occur?

• In the mitochondrial matrix of eukaryotic cells.

• Near the inner mitochondrial membrane, where electron transport occurs.

4. What is the main purpose of the citric acid cycle?

• Extract energy from acetyl-CoA through oxidation.

• Transfer electrons to NAD⁺ and FAD, forming NADH and FADH₂.

What are the products of one turn of the citric acid cycle?

• 3 NADH

• 2 CO₂

• 1 FADH₂

• 1 GTP

• NCGF

• no care, great friends

How many times does the citric acid cycle turn per glucose?

One glucose produces two pyruvate, which form two acetyl-CoA.

One glucose produces two pyruvate, which form two acetyl-CoA.

• 6 NADH.

• 4 CO₂.

• 2 FADH₂.

• 2 GTP.

What happens to pyruvate before entering the TCA cycle?

• Pyruvate enters the mitochondrial matrix.

• Pyruvate dehydrogenase (PDH) converts it into acetyl-CoA.

What are the products of the PDH reaction?

• Acetyl-CoA.

• NADH.

• CO₂.

Why is acetyl-CoA important?

• Carries a 2-carbon acetyl group into the TCA cycle.

• Contains a high-energy thioester bond.

How is PDH regulated?

• PDH kinase: Phosphorylates and inactivates PDH.

• PDH phosphatase: Removes phosphate and activates PDH.

What signals reduce PDH activity?

• High ATP, NADH, and acetyl-CoA.

• Indicate that energy and products are abundant.

What are the three phases of the TCA cycle?

• Phase 1: Formation of isocitrate (6 carbons).

• Phase 2: Two decarboxylations (6C → 5C → 4C).

• Phase 3: Regeneration of oxaloacetate (4 carbons).

Why is the TCA pathway called a cycle?

• Oxaloacetate is used in the first reaction.

• It is regenerated in the final reaction.

What happens to the carbons entering the TCA cycle?

• A 2-carbon acetyl group enters.

• Two CO₂ molecules are released each turn.

• The incoming acetyl carbons are not the two carbons released during that same turn.

What happens in step 1?

• Enzyme: Citrate synthase.

• Acetyl-CoA (2C) + oxaloacetate (4C) → citrate (6C).

• Energy comes from breaking the thioester bond.

What happens in step 2?

• Enzyme: Aconitase.

• Citrate → isocitrate.

• Rearranges the –OH group to prepare for oxidation.

What happens in step 3?

• Enzyme: Isocitrate dehydrogenase.

• Isocitrate (6C) → α-ketoglutarate (5C).

• Produces NADH and CO₂.

What happens in step 4?

• Enzyme: α-Ketoglutarate dehydrogenase.

• α-Ketoglutarate (5C) → succinyl-CoA (4C).

• Produces NADH and CO₂.

What is oxidative decarboxylation?

• A molecule is oxidized while CO₂ is removed.

• Electrons are transferred to NAD⁺, producing NADH.

What happens in step 5?

• Enzyme: Succinyl-CoA synthetase.

• Succinyl-CoA → succinate.

• Produces GTP through substrate-level phosphorylation.

What happens in step 6?

• Enzyme: Succinate dehydrogenase.

• Succinate → fumarate.

• Produces FADH₂.

What happens in step 7?

• Enzyme: Fumarase.

• Fumarate → malate.

• Adds water across a double bond.

What happens in step 8?

• Enzyme: Malate dehydrogenase.

• Malate → oxaloacetate.

• Produces NADH, completing the cycle.

Which TCA steps produce NADH?

• Steps 3, 4, and 8.

• Total: 3 NADH per turn.

Which TCA step produces FADH₂?

• Step 6.

• Succinate is oxidized to fumarate.

Which TCA step produces GTP?

• Step 5.

• Succinyl-CoA is converted into succinate.

What is substrate-level phosphorylation in the TCA cycle?

• Direct production of GTP using energy from a high-energy intermediate.

• Occurs during step 5.

How many ATP equivalents are produced per TCA turn according to your lecture?

• 3 NADH × 3 ATP = 9 ATP.

• 1 FADH₂ × 2 ATP = 2 ATP.

• 1 GTP = 1 ATP.

• Total = 12 ATP equivalents.

How many ATP equivalents are produced by two TCA turns?

• 12 × 2 = 24 ATP equivalents.

• This is the lecture's accounting method.

Which TCA steps are rate-limiting or major control points?

• Step 1: Citrate synthase.

• Step 3: Isocitrate dehydrogenase.

• Step 4: α-Ketoglutarate dehydrogenase.

How is the TCA cycle mainly regulated?

• Substrate availability.

• Product inhibition.

• Inhibition by other pathway intermediates.

⭐ What happens when NADH levels are high?

• NADH inhibits important TCA enzymes.

• The cycle slows because the cell has abundant reducing power.

Why does high ATP slow the TCA cycle?

• High ATP signals sufficient cellular energy.

• NADH is used less rapidly, allowing it to accumulate and inhibit the cycle.

. What happens when cellular energy is low?

• Low ATP or high AMP signals increased energy demand.

• TCA activity is favored to support ATP production.

Which TCA reactions are inhibited by NADH?

• Steps 3, 4, and 8, as emphasized in your lecture.

• NADH also inhibits pyruvate oxidatio

What is the importance of the NADH/NAD⁺ ratio?

• High NADH/NAD⁺: Slows the cycle.

• Low NADH/NAD⁺: Favors oxidation and continued cycle activity.

How many ATP equivalents are produced per glucose according to the lecture?

• Glycolysis: 8 ATP equivalents.

• PDH: 6 ATP equivalents.

• TCA cycle: 24 ATP equivalents.

• Total = 38 ATP equivalents.

What is the role of NADH and FADH₂?

• Carry high-energy electrons.

• Donate electrons to the electron transport chain for ATP production.

. Why is oxygen important for continued aerobic metabolism?

• Oxygen is the final electron acceptor in the electron transport chain.

• Allows NADH and FADH₂ to be reoxidized.