Krebs Cycle Intermediates

The Krebs Cycle, also known as the citric acid cycle, is essential for energy production in cells. Its intermediates, like citrate and α-ketoglutarate, play crucial roles in metabolism, linking energy generation to various biochemical pathways.

1. Citrate

   • Formed from the condensation of acetyl-CoA and oxaloacetate, catalyzed by citrate synthase.
   • Acts as a key intermediate that initiates the Krebs Cycle.
   • Plays a role in regulating metabolic pathways, including fatty acid synthesis and gluconeogenesis.

2. Isocitrate

   • Converted from citrate through the action of aconitase, involving a cis-aconitate intermediate.
   • Isocitrate is a substrate for oxidative decarboxylation, producing α-ketoglutarate.
   • Important for the production of NADH, which is crucial for ATP generation.

3. α-Ketoglutarate

   • Formed from isocitrate by isocitrate dehydrogenase, releasing CO2 and generating NADH.
   • Serves as a key intermediate in amino acid metabolism and neurotransmitter synthesis.
   • Plays a role in the regulation of the Krebs Cycle and energy production.

4. Succinyl-CoA

   • Produced from α-ketoglutarate through the action of α-ketoglutarate dehydrogenase, also releasing CO2 and generating NADH.
   • Contains a high-energy thioester bond, which is used to generate GTP or ATP in the next step.
   • Important for heme synthesis, as it is a precursor for porphyrin synthesis.

5. Succinate

   • Formed from succinyl-CoA by succinyl-CoA synthetase, producing GTP or ATP.
   • Undergoes oxidation to fumarate, generating FADH2, which contributes to the electron transport chain.
   • Plays a role in the regulation of metabolic pathways and energy production.

6. Fumarate

   • Produced from succinate by the action of succinate dehydrogenase, which is also part of the electron transport chain.
   • Fumarate can be hydrated to form malate, continuing the cycle.
   • Involved in the urea cycle and amino acid metabolism.

7. Malate

   • Formed from fumarate through the action of fumarase.
   • Converted back to oxaloacetate by malate dehydrogenase, generating NADH.
   • Plays a role in gluconeogenesis and the transport of reducing equivalents.

8. Oxaloacetate

   • Regenerated from malate, completing the Krebs Cycle.
   • Combines with acetyl-CoA to form citrate, thus linking the cycle back to the beginning.
   • Important for amino acid synthesis and serves as a key metabolic intermediate in various pathways.