IDH1

Isocitrate dehydrogenase 1 (NADP+), soluble is an is_associated_with::enzyme that in humans is encoded by the IDH1 is_associated_with::gene.

Function
is_associated_with::Isocitrate dehydrogenases catalyze the oxidative decarboxylation of isocitrate to 2-oxoglutarate. These enzymes belong to two distinct subclasses, one of which uses NAD+ as the electron acceptor and the other NADP+. Five isocitrate dehydrogenases have been reported: three NAD+-dependent isocitrate dehydrogenases, which localize to the mitochondrial matrix, and two NADP+-dependent isocitrate dehydrogenases, one of which is mitochondrial and the other predominantly cytosolic. Each NADP+-dependent isozyme is a homodimer. The protein encoded by this gene is the NADP+-dependent isocitrate dehydrogenase found in the is_associated_with::cytoplasm and is_associated_with::peroxisomes. It contains the PTS-1 is_associated_with::peroxisomal targeting signal sequence. The presence of this enzyme in peroxisomes suggests roles in the regeneration of NADPH for intraperoxisomal reductions, such as the conversion of 2,4-dienoyl-CoAs to 3-enoyl-CoAs, as well as in peroxisomal reactions that consume 2-oxoglutarate, namely the alpha-is_associated_with::hydroxylation of is_associated_with::phytanic acid. The cytoplasmic enzyme serves a significant role in cytoplasmic NADPH production.

Clinical relevance
Mutations in this gene have been shown to cause metaphyseal is_associated_with::chondromatosis with is_associated_with::aciduria.

Mutations in IDH1 are also implicated in cancer. Originally, mutations in IDH1 were detected in an integrated genomic analysis of human glioblastoma multiforme. Since then it has become clear that mutations in IDH1 and its homologue IDH2 are among the most frequent mutations in diffuse gliomas, including diffuse astrocytoma, anaplastic astrocytoma, oligodendroglioma, anaplastic oligodendroglioma, oligoastrocytoma, anaplastic oligoastrocytoma, and secondary glioblastoma. Watanabe and coworkers could show that mutations in IDH1 are often the first hit in the development of diffuse gliomas, suggesting ‘’IDH1’’ mutations as key events in the formation of these brain tumors. IDH1 mutations are associated with a prolonged survival. Glioblastomas with a wild-type IDH1 gene have a median overall survival of only 1 year, whereas IDH1-mutated glioblastoma patients have a median overall survival of over 2 years.

In addition to being mutated in diffuse gliomas, IDH1 has also been shown to harbor mutations in human acute myeloid leukemia.