Isocitrate dehydrogenase enzymes catalyze the oxidative decarboxylation of isocitrate to produce alfa ketoglutarate. The human genome has 5 IDH genes coding for 3 IDH enzymes. The IDH1 and IDH2 require nicotinamide adeninedinucleotide phosphate (NADP) as co-substrate, whereas IDH3 require nicotinamide adenine dinucleotide (NAD). The IDH 2 and 3 are localized in mitochondria and are actively involved in the citric acid cycle (TCA) for energy production in contrast, IDH1 is localized in cytoplasm and peroxisomes where it generates NADPH, reduced form of NADP for biosynthetic and other types of reaction (1). Since alfa KG and NADPH both are intermediately substrate for a number of cellular process, which allows the possibility of oncogenic or tumor suppressive activities of IDH1.
The high throughput DNA sequencing is providing an unprejudiced picture of cancer associated mutations across the genome. The identification of mutations in a specific isoform of IDH1 gene in glioblastoma multiforme suggest that this enzyme may be promoting oncogenesis (2). Heterozygous IDH1 mutations have been identified in up to 80% of certain types of glioblastoma multifome and remarkably all these mutations are confined to a single residue, conserved in all three IDH enzymes, Arginine 132 to histidine substitution. Additionally five more mutations have been identified (Ser, Cys, Gly, Val and Leu) which suggest that IDH1 may be a atypical tumor suppressor as a result of mutations causing a loss of function or an oncogne in which the mutation causes gain in function (1). The mutant IDH1 enzyme dimerizes with wild type IDH1 to form an inactive complex in hypoxia inducible factor mediated oncogenic pathway thus causing a decrease in alfa KG and dioxygenase family enzymes that catalyses the hydroxylation of HIF and make it susceptible to degradation (3). Other Arginine residues Arg100 and 109 of human IHD1 are implicated in isocitrate binding and mutations at these sites resulted in inactive enzyme (4). The mutations at Arg132 causes impairments in the affinity of IDH1 for its substrate and inhibit the wild type IDH1 activity by formation of catalytically inactive heterodimers (5). Thus IDH1appears to function as a tumor suppressor but mutational inactivated protein contribute tumorogenesis in part through induction of hypoxia inducible factor (5). IDH1 is a 414 amino acid protein (51kDa) located on chromosome 2q.33.3a and contains a PTS peroxisomal signal targeting sequence.
The IDH1-selective antibodies were generated against conserved sequences that are unique to human and rat/mouse IDH1protein. The IDH1-selective antibodies are affinity purified against immobilized antigen based affinity chromatography which yielded epitope-specific antibodies. The IDH1 antibodies label a 50kDa IDH1 protein in IDH1 protein in Western blot using Western blot positive control for IDH1 (PC-IDH1). Anti-IDH1-selective antibodies can be conjugated to FITC or other fluorophores and enzymes (HRP and Alkaline phosphatase) for direct application in IHC and confocal microscopy at a nominal charge. Limited quantities of Western blot positive controls for IDH1 (PC-IDH1) and antigenic blocking peptide (P-IDH1) for IDH-101AP antibody are also available, please inquire availability before placing orders. FabGennix Inc. also provides antibodies to many cancer related proteins and markers, for a complete listing please visit www.fabgennix.com. FabGennix Inc employs cyclic peptide methodology for generating antibodies, which results in higher titer and specificity.
For research use only, not for diagnostic or therapeutic use.
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