isocitrátdehidrogenáz

Isocitrate dehydrogenase, often abbreviated as IDH, is an enzyme that catalyzes the oxidative decarboxylation of isocitrate to alpha-ketoglutarate. This reaction is a crucial step in the citric acid cycle, also known as the Krebs cycle or TCA cycle, which is a central metabolic pathway for energy production in aerobic organisms. The enzyme plays a key role in the generation of reducing equivalents in the form of NADH or NADPH, depending on the specific isoform.

There are several isoforms of isocitrate dehydrogenase, broadly categorized into NAD+-dependent and NADP+-dependent forms. The NAD+-dependent form is primarily located in the mitochondria and is involved in the citric acid cycle for ATP production. The NADP+-dependent forms are found in both the cytoplasm and mitochondria, with the cytoplasmic form being particularly important in the pentose phosphate pathway, which generates NADPH for reductive biosynthesis and antioxidant defense.

Mutations in isocitrate dehydrogenase genes, particularly IDH1 and IDH2, have been strongly implicated in the development and progression of various cancers, notably gliomas and acute myeloid leukemia. These mutations often lead to the production of an oncometabolite, 2-hydroxyglutarate (2-HG), which can interfere with cellular differentiation and epigenetic regulation, promoting tumorigenesis. The study of IDH enzymes and their role in cancer has opened avenues for targeted therapies.