TCA Cycle
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Key Points
- TCA cycle
- Etymology
- Citrate has 3 carboxylic acid groups (TCA cycle =TriCarboxylic Acid cycle)
- Also called Krebs cycle or Citric Acid cycle
- Discovered by Hans Krebs (Krebs cycle)
- 1st step produces citrate (citric acid cycle)
- Summary
- TCA cycle is a metabolic pathway that metabolizes biomolecules to produce high energy products
- High energy products: NADH, FADH2, and GTP
- NADH and FADH2 are used to produced ATP in the Electron Transport Chain
- GTP can be converted to ATP at no energy cost
- High energy products: NADH, FADH2, and GTP
- Central hub
- Protein, Carbs, and Fats can be all metabolized and fed into the TCA for energy production
- Starting molecule: acetyl-CoA
- Can be produced from pyruvate (final product of carbohydrate metabolism)
- Can also be produced from the metabolism of fats and proteins
- Produces CO2
- Carbons from acetyl-CoA are oxidized to CO2
- Allows for energy payoff as high energy products
- The Carbons that are oxidized in a given cycle actually come from oxaloacetate. However, the carbons from acetyl-CoA get integrated into oxaloacetate and are then oxidized over the course of a few rounds of the TCA cycle
- Carbons from acetyl-CoA are oxidized to CO2
- Overall reaction: Acetyl-CoA + 3NAD+ + FAD + GDP + Pi +2H2O → 2CO2 + CoA-SH + 3NADH + 3H+ + FADH2 + GTP
- TCA cycle is a metabolic pathway that metabolizes biomolecules to produce high energy products
- Location
- Occurs in the mitochondrial matrix
- Part of aerobic respiration, coupled with oxidative phosphorylation
- Inhibited in anaerobic conditions
- Part of aerobic respiration, coupled with oxidative phosphorylation
- Occurs in the mitochondrial matrix
- Reaction steps
- oxaloacetate + acetyl-CoA →[citrate synthase] citrate
- Irreversible (regulatory site)
- Acetyl group is linked to CoA by a high energy thioester bond
- Breaking that bond is very exergonic, making the overall delta G very negative
- Oxaloacetate is normally present at low concentrations, so this negative delta G helps drag the reaction forward
- Thioesters may have played the role of ATP in the primordial stages of life’s development
- Breaking that bond is very exergonic, making the overall delta G very negative
- Acetyl group is linked to CoA by a high energy thioester bond
- Irreversible (regulatory site)
- citrate → [aconitase] isocitrate
- Intermediate: cis-aconitate
- isocitrate → [isocitrate dehydrogenase] alpha-ketoglutarate
- Produces 1 NADH and 1 CO2
- Irreversible (regulatory site)
- alpha-ketoglutarate → [alpha-ketoglutarate dehydrogenase] succinyl-CoA
- succinyl-CoA linked by high energy thioester bond
- Some of the energy from oxidizing carbon is preserved in this bond
- This energy is used to power GTP production in the next step
- Some of the energy from oxidizing carbon is preserved in this bond
- Produces 1 NADH and 1 CO2
- Irreversible (regulatory site)
- succinyl-CoA linked by high energy thioester bond
- succinyl-CoA → [succinyl-CoA synthetase] succinate
- Produces 1 GTP
- 1 GTP = 1 ATP
- Produces 1 GTP
- succinate → [succinate dehydrogenase] fumarate
- Produces 1 FADH2
- fumarate → [fumarase] malate
- malate → [malate dehydrogenase] oxaloacetate
- Produces 1 NADH
- Oxaloacetate can then recycle back into the first step of the cycle: Acetyl-CoA + oxaloacetate → citrate
- Cycle repeats
- oxaloacetate + acetyl-CoA →[citrate synthase] citrate
- Regulation
- Regulation is based on the energy needs of the cell
- TCA cycle is primarily regulated allosterically at the irreversible steps
- TCA slows down (inhibition)
- Downregulated by molecules that are present at higher concentrations when the cell has plenty of energy
- NADH, ATP and other products of the pathway
- Downregulated by molecules that are present at higher concentrations when the cell has plenty of energy
- TCA speeds up (activation)
- Upregulated by molecules/ions that are present at higher concentrations when the cell needs more energy
- ADP, NAD+
- Might be framed as a high ADP/ATP and high NAD+/NADH ratio
- Ca2+
- Ca2+ causes muscle contraction and a contracting muscle requires energy, so Ca2+ upregulates TCA cycle
- ADP, NAD+
- Upregulated by molecules/ions that are present at higher concentrations when the cell needs more energy
- Etymology