TCA cycle

Location of TCA cycle

Mitochondrial matrix

TCA oxygen requirement

Requires oxygen indirectly because O₂ is the final electron acceptor in the ETC

TCA cycle main goal

Extract energy from acetyl-CoA and make NADH, FADH₂, ATP, and CO₂

Number of TCA turns per glucose

Two turns per glucose because one glucose makes 2 pyruvate which makes two acetyl-CoA

Pyruvate to acetyl-CoA reaction

Pyruvate + CoA-SH + NAD⁺ → Acetyl-CoA + CO₂ + NADH

Pyruvate dehydrogenase complex enzyme name

Pyruvate Dehydrogenase Complex (PDC)

Pyruvate dehydrogenase inhibited by

High energy signals ATP NADH and Acetyl-CoA

Pyruvate dehydrogenase activated by

Low energy signals NAD⁺ AMP and CoA-SH

Pyruvate dehydrogenase covalent regulation

Phosphorylation inactivates the complex and dephosphorylation activates it

Step 1 reaction

Acetyl-CoA + Oxaloacetate → Citrate

Step 1 details

• Uses water

• releases CoA-SH

• exergonic and irreversible

Step 1 regulation

Inhibited by Succinyl-CoA, NADH and, ATP

Step 2 reaction

Citrate → Isocitrate

Step 2 details

• Isomerization step

• no ATP or reduced coenzymes produced

• rearranges to prepare for oxidation

Step 3 reaction

Isocitrate → α-Ketoglutarate

Step 3 details

• Makes NADH

• releases CO₂

• exergonic, not reversible

• Major control point of the TCA cycle

Step 3 regulation

• activated by ADP and NAD⁺

• inhibited by ATP and NADH

Step 4 enzyme (TCA)

α-Ketoglutarate dehydrogenase complex

Step 4 details

• Makes NADH

• releases CO₂

• exergonic, not reversible

Step 4 regulation

• activated by AMP

• inhibited by NADH and Succinyl-CoA

Step 5 reaction

Succinyl-CoA → Succinate

Step 5 details

• Produces GTP or ATP

• releases CoA-SH

• Substrate-level phosphorylation

Step 6 reaction

Succinate → Fumarate

Step 6 details

• produces FADH₂

• enzyme is also Complex II of the electron transport chain

• happens in the inner mitochondrial membrane

Step 7 reaction

Fumarate → Malate

Step 7 details

• uses water

• does not produce ATP or reduced coenzymes

Step 8 reaction

Malate → Oxaloacetate

Step 8 products

• produces NADH

• regenerates oxaloacetate

Products per one TCA turn

1 turn per acetyl-coa

• 3 NADH

• 1 FADH₂

• 1 ATP or GTP

• 2 CO₂

Products per glucose in TCA

2 turns per glucose

• 6 NADH

• 2 FADH₂

• 2 ATP

• 4 CO₂

High energy effect on TCA

High ATP NADH and Succinyl-CoA turn the TCA cycle off

Low energy effect on TCA

High ADP AMP and NAD⁺ turn the TCA cycle on

Enzyme class of dehydrogenases in TCA

All dehydrogenases (steps 3 4 6 and 8) are oxidoreductases

Enzyme class of isomeras

aconitase

Enzyme class of lyases

Fumarate (hydratase) and citrate synthase

Enzyme class of ligase

succinyl-CoA synthetase

Purpose of TCA cycle

Completely oxidize acetyl-CoA release CO₂ make NADH and FADH₂ for the ETC and make 1 ATP or GTP

Super short TCA summary

Each acetyl-CoA gives 3 NADH 1 FADH₂ 1 ATP and 2 CO₂

NADH-forming steps in TCA

Steps 3, 4 and 8

FADH₂-forming step in TCA

Step 6

ATP-forming step in TCA

Step 5 produces ATP or GTP