logo
AAT Bioquest

How does the citric acid cycle work?

Posted November 6, 2023


Answer

The citric acid occurs within the mitochondria and releases large quantities of energy during aerobic respiration by donating electrons to 3 NADH and 1 FADH molecule. These molecules donate their electrons to the ETC, forming the required proton gradient to fuel ATP synthesis. The citric acid cycle is initiated when acetyl-CoA binds with a four-carbon molecule known as oxaloacetate. This generates citric acid as a byproduct, which contains six carbon atoms. The citric acid is then converted to isocitrate through the removal and then the addition of H20 molecules. Next, isocitrate is oxidized via isocitrate dehydrogenase and a carbon dioxide molecule is lost as waste in the process, forming alpha-ketoglutarate. NAD+ also becomes reduced to produce NADH. Alpha-ketoglutarate is then oxidized via alpha-ketoglutarate dehydrogenase and loses another carbon dioxide molecule in the process to form succinyl CoA. NAD+ is again reduced to NADH. Next, the phosphate group is transferred to the CoA of succinyl CoA replacing CoA to form the four-carbon molecule succinate. Succinate then becomes oxidized via succinate dehydrogenase to produce an fumarate, which is also a four-carbon molecule. In this step, 2 electrons are transferred to FAD, producing a FADH2 molecule for the  transport of electrons to the ETC. Succinate dehydrogenase is a particularly important enzyme as it is the only enzyme involved in both the TCA cycle and the ETC. Water is then added to the fumarate molecule, forming malate, which is another four-carbon molecule. The final step of the TCA cycle regenerates oxaloacetate through the oxidation of malate via malate hydrogenase. Another NAD+ molecule is reduced to NADH in the process as well. It is important to note that for each glucose molecule, the TCA cycle reactions occur twice since glycolysis forms 2 pyruvate molecules when it splits glucose. 

Additional resources

Citric Acid Cycle

Cellular Processes

Cell Signaling

PhosphoWorks™ Fluorimetric ATP Assay Kit