From the Guidelines
The Krebs cycle, also known as the citric acid cycle or tricarboxylic acid (TCA) cycle, is a series of chemical reactions that occurs in the mitochondria of cells to generate energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins. This cycle is a central metabolic pathway that connects carbohydrate, fat, and protein metabolism. It begins when acetyl-CoA combines with oxaloacetate to form citric acid, then proceeds through eight steps, regenerating oxaloacetate at the end. During these reactions, the cycle produces three NADH molecules, one FADH2 molecule, and one GTP (or ATP) molecule per acetyl-CoA molecule. These high-energy electron carriers (NADH and FADH2) then donate electrons to the electron transport chain, which ultimately generates ATP through oxidative phosphorylation. The Krebs cycle also provides intermediates for various biosynthetic pathways, including amino acid synthesis. This process is aerobic, requiring oxygen as the final electron acceptor, and represents a critical step in cellular respiration between glycolysis and the electron transport chain.
Key Points
- The Krebs cycle is a critical step in cellular respiration, generating energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins 1.
- The cycle produces high-energy electron carriers (NADH and FADH2) that donate electrons to the electron transport chain, ultimately generating ATP through oxidative phosphorylation.
- The Krebs cycle provides intermediates for various biosynthetic pathways, including amino acid synthesis.
- This process is aerobic, requiring oxygen as the final electron acceptor, and represents a critical step in cellular respiration between glycolysis and the electron transport chain.
Clinical Significance
The Krebs cycle plays a crucial role in maintaining energy homeostasis in the body. Dysregulation of the Krebs cycle has been implicated in various diseases, including diabetes and cancer. Understanding the Krebs cycle is essential for developing effective therapeutic strategies for these diseases. For example, citrate, an intermediate of the Krebs cycle, is used as an anticoagulant in dialysis procedures and can provide energy substrates to patients undergoing kidney replacement therapy 1.
Metabolic Pathways
The Krebs cycle is connected to other metabolic pathways, including glycolysis, the electron transport chain, and fatty acid metabolism. The cycle is regulated by various enzymes and cofactors, including ATP, NADH, and FADH2. The Krebs cycle is also influenced by hormonal regulation, including insulin and glucagon, which play a crucial role in maintaining glucose homeostasis 1.
In summary, the Krebs cycle is a critical metabolic pathway that generates energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins. Understanding the Krebs cycle is essential for maintaining energy homeostasis and developing effective therapeutic strategies for various diseases.
From the Research
Overview of the Krebs Cycle
- The Krebs cycle, also known as the citric acid or tricarboxylic acid (TCA) cycle, is a central metabolic pathway that plays a crucial role in cellular bioenergetics 2.
- It is a key process by which cells generate energy from the food they consume, and it is essential for the oxidation of nutrients to support cellular functions 3.
Function and Regulation
- The TCA cycle is a dynamic process that can be regulated to meet the needs of different cell types and states 2.
- It is involved in the metabolism of carbohydrates, fats, and amino acids, and it produces ATP, NADH, and other important metabolites 4, 3.
- The cycle is also important for the regulation of macrophage activation and effector phenotypes, and it plays a role in the control of immune responses 4.
Variations and Related Pathways
- A reverse Krebs cycle, also known as the reductive carboxylic acid cycle, has been identified in some photosynthetic organisms, and it is thought to be an ancient mechanism for CO2 assimilation 5.
- The TCA cycle is also connected to other metabolic pathways, and it can be reprogrammed in response to cellular stress or other challenges 6.
Importance and Implications
- The Krebs cycle is a critical component of cellular metabolism, and it has important implications for our understanding of cellular biology and disease 2, 6.
- Dysregulation of the TCA cycle has been implicated in a range of diseases, including cancer and metabolic disorders, and further research is needed to understand its role in these conditions 2, 6.