The regulatory enzyme involved in the citric acid cycle also known as the Krebs cycle or the tricarboxylic acid cycle is isocitrate dehydrogenase IDH . This enzyme catalyzes the oxidative decarboxylation of isocitrate to alpha-ketoglutarate, generating NADH and CO2 in the process. IDH plays a crucial role in controlling the rate of the citric acid cycle and, consequently, the production of ATP.Isocitrate dehydrogenase is regulated through allosteric inhibition and activation. The enzyme is inhibited by high levels of ATP and NADH, which signal that the cell has sufficient energy and does not need to produce more. Conversely, IDH is activated by high levels of ADP and NAD+, which indicate that the cell requires more energy. This feedback mechanism ensures that the citric acid cycle operates at an appropriate rate to meet the cell's energy demands.The absence or excess of isocitrate dehydrogenase can lead to metabolic disorders. If IDH is absent or its activity is significantly reduced, the citric acid cycle cannot function efficiently, leading to a decrease in ATP production. This can result in various metabolic disorders, such as Leigh syndrome, which is a severe neurological disorder caused by defects in mitochondrial energy production.On the other hand, if there is an excess of IDH or its activity is abnormally high, it can lead to an overproduction of ATP and NADH. This can cause an imbalance in cellular energy metabolism and may contribute to the development of certain types of cancer. For example, mutations in the IDH1 and IDH2 genes have been implicated in the development of gliomas, acute myeloid leukemia, and other malignancies. These mutations often result in the production of an oncometabolite, 2-hydroxyglutarate 2-HG , which can alter cellular metabolism and promote tumorigenesis.In conclusion, isocitrate dehydrogenase is a key regulatory enzyme in the citric acid cycle, and its inhibition mechanism involves allosteric regulation by ATP, NADH, ADP, and NAD+. The absence or excess of this enzyme can lead to metabolic disorders, highlighting the importance of maintaining proper enzyme levels and activity for cellular energy metabolism.