IDH1(R132C) His Tag Protein, Human

IDH1 (Isocitrate Dehydrogenase 1) is a key metabolic enzyme located in the cytoplasm and peroxisomes. Its primary physiological function is to catalyze the oxidative decarboxylation of isocitrate to produce alpha-ketoglutarate (α-KG), while concurrently reducing NADP+ to NADPH. This reaction is crucial for cellular metabolism, as it links the tricarboxylic acid (TCA) cycle with lipid metabolism and provides NADPH, a major reducing agent essential for antioxidant defense and anabolic biosynthesis.

A seminal discovery in cancer biology revealed that specific heterozygous somatic mutations in the IDH1 gene, most commonly at the R132 residue, are frequent drivers in several cancers. These include gliomas (especially secondary glioblastoma and oligodendroglioma), acute myeloid leukemia (AML), cholangiocarcinoma, and chondrosarcomas. The mutant enzyme acquires a neomorphic activity: instead of producing α-KG, it reduces α-KG to D-2-hydroxyglutarate (D-2HG). This oncometabolite, D-2HG, accumulates to high levels and functions as a competitive inhibitor of multiple α-KG-dependent dioxygenases. This inhibition leads to profound epigenetic dysregulation (via inhibition of histone and DNA demethylases) and blockade of cellular differentiation, thereby promoting tumorigenesis.