TCA Cycle Assays

The citric acid cycle, also known as the Krebs cycle or Tricarboxylic acid (TCA) cycle, is a series of biochemical steps that occur in the cells of all aerobic organisms. This pathway is responsible for the production of cellular energy in the form of adenosine triphosphate (ATP). In this blog post, we will discuss the Krebs cycle in detail, and look at how defects in this pathway can lead to disease.

What role does Krebs cycle play?

Aerobic respiration is the process by which cells produce energy from glucose and oxygen. This process occurs in the mitochondria, and involves a series of steps known as the citric acid cycle or (TCA) Tricarboxylic acid cycle. The citric acid cycle is also known as the Krebs cycle, named after Hans Adolf Krebs, who first described this pathway in 1937.

The citric acid cycle is a series of eight chemical reactions that take place in the mitochondria of cells. These reactions convert glucose and oxygen into adenosine triphosphate (ATP), water, and carbon dioxide. The citric acid cycle is responsible for the production of cellular energy in the form of ATP. Under hypoxic conditions, they switch to anaerobic respiration. Anaerobic respiration is less efficient than aerobic respiration, and results in the production of lactic acid. Lactic acid build-up can lead to muscle fatigue and cramping.

Krebs cycle related products

Krebs cycle steps

The citric acid cycle is a series of eight chemical reactions that take place in the mitochondria of cells. These reactions convert glucose and oxygen into ATP, water, and carbon dioxide. The citric acid cycle can be divided into three phases: phase I, phase II, and phase III. Phase I of the citric acid cycle is responsible for the conversion of glucose to two molecules of acetyl CoA. Phase II of the citric acid cycle is responsible for the conversion of acetyl CoA to two molecules of citrate. Phase III of the citric acid cycle is responsible for the conversion of citrate to two molecules of ATP.

Role of citric acid cycle enzymes

Enzymes are required to catalyze each reaction in the Krebs cycle. These enzymes are all embedded in the inner mitochondrial membrane.

- Citrate synthase converts citrate to acetyl coA. Acetyl CoA is involved in the synthesis of fatty acids and cholesterol.

- Aconitase converts citrate to isocitrate. Isocitrate is involved in the regulation of blood sugar levels and has anti-inflammatory effects.

- Isocitrate dehydrogenase converts isocitrate to alpha-ketoglutarate. Alpha ketoglutarate is a precursor for the synthesis of glutamine, which is an important amino acid.

- Alpha-ketoglutarate dehydrogenase converts alpha-ketoglutarate to succinyl-CoA. Succinyl CoA is used in the production of cholesterol and other steroids.

- Succinate dehydrogenase converts succinate to fumarate. Fumarate is involved in the synthesis of purines, pyrimidines, and other important molecules.

- Fumarase converts fumarate to malate. Malate plays a role in the citric acid cycle by shuttling electrons between the cytochrome and electron transport chain.

- Malate dehydrogenase converts malate to oxaloacetate. Oxaloacetate plays a role in the synthesis of amino acids and glucose.

- Oxaloacetate is converted back to citrate by citrate synthase, completing the cycle.

Net products of citric acid cycle

The citric acid cycle produces a net total of three molecules of ATP. In addition, the cycle also produces water and carbon dioxide. The citric acid cycle produces two molecules of NADH and one molecule of FADH. NADH and FADH are important molecules in the citric acid cycle. NADH is used to power the citrate synthase reaction, while FADH is used to power the succinate dehydrogenase reaction. Electrons are transferred from NADH and FADH to the electron transport chain, which results in the production of ATP.

Krebs cycle associated diseases and the potential of TCA cellular therapy

Deficiencies in citric acid cycle enzymes can lead to diseases such as paraganglioma and Leigh syndrome. Cancer cells have a high rate of metabolism and require large amounts of energy to grow and divide. As a result, cancer cells have an increased demand for citric acid cycle enzymes. This can lead to the overproduction of citrate, which can then inhibit the function of other enzymes in the pathway, ultimately resulting in cell death. Therefore, defects in the Krebs cycle can also cause cancer.

TCA cellular therapy is a promising new treatment method that targets defective citric acid cycle enzymes. This type of therapy uses genetically-modified cells to correct defects in the citric acid cycle. TCA cellular therapy involves the injection of mitochondria-enriched cells into the patient's body. These cells provide new mitochondria to the patient, and help to restore energy production.

TCA cellular therapy is still in the early stages of development, and more research is needed to determine its safety and efficacy. However, there are some promising examples of TCA cellular therapy that have been reported in the literature.

One example of TCA cellular therapy is the use of genetically-modified cells to correct a defect in the citric acid cycle enzyme succinate dehydrogenase (SDH). SDH mutations have been linked to paraganglioma, a rare type of cancer. In this study, genetically-modified cells were used to correct the SDH mutation in patient-derived tumor cells. The results of this study showed that TCA cellular therapy was able to correct the SDH mutation and improve citric acid cycle function.

Another example of TCA cellular therapy is the use of genetically-modified cells to correct a defect in the citric acid cycle enzyme aconitase. Aconitase mutations have been linked to Leigh syndrome, a rare neurological disorder. In this study, genetically-modified cells were used to correct the aconitase mutation in patient-derived brain cells. The results of this study showed that TCA cellular therapy was able to correct the aconitase mutation and improve citric acid cycle function.

Citrullinemia is caused by a defect in citrate synthase. This disease results in the accumulation of citrulline in the blood and can lead to death. TCA cellular therapy involves the injection of citrate synthase enzyme into cells. This enzyme catalyzes the conversion of citrulline to arginine, which eliminates the build-up of this molecule and restores normal function.

The citric acid cycle is a vital pathway in the production of cellular energy. This article provides a flowchart of Krebs cycle and an overview of the enzymes involved in each step. It also discusses the potential of TCA cellular therapy for diseases associated with the citric acid cycle.