Products

Enzymes for Research, Diagnostic and Industrial Use

IDH


Official Full Name
IDH
Background
Isocitrate dehydrogenase (IDH) (EC 1.1.1.42) and (EC 1.1.1.41) is an enzyme that catalyzes the oxidative decarboxylation of isocitrate, producing alpha-ketoglutarate (α-ketoglutarate) and CO2. This is a two-step process, which involves oxidation of isocitrate (a secondary alcohol) to oxalosuccinate (a ketone), followed by the decarboxylation of the carboxyl group beta to the ketone, forming alpha-ketoglutarate. In humans, IDH exists in three isoforms: IDH3 catalyzes the third step of the citric acid cycle while converting NAD+ to NADH in the mitochondria. The isoforms IDH1 and IDH2 catalyze the same reaction outside the context of the citric acid cycle and use NADP+ as a cofactor instead of NAD+. They localize to the cytosol as well as the mitochondrion and peroxisome.
Synonyms
isocitrate dehydrogenase (NADP+); oxalosuccinate decarboxylase; oxalsuccinic decarboxylase; isocitrate (NADP) dehydrogenase; isocitrate (nicotinamide adenine dinucleotide phosphate) dehydrogenase; NADP-specific isocitrate dehydrogenase; NADP-linked isocitrate dehydrogenase; NADP-dependent isocitrate dehydrogenase; NADP isocitric dehydrogenase; isocitrate dehydrogenase (NADP-dependent); NADP-dependent isocitric dehydrogenase; triphosphopyridine nucleotide-linked isocitrate dehydrogenase-oxalosuccinate carboxylase; NADP+-linked isocitrate dehydrogenase; IDH (ambiguous); dual-cofactor-specific isocitrate dehydrogenase; NADP+-ICDH; NADP+-IDH; IDP; IDP1; IDP2; IDP3

Catalog
Product Name
EC No.
CAS No.
Source
Price
CatalogNATE-1649
EC No.
CAS No.
SourceE. coli
CatalogEXWM-0327
EC No.EC 1.1.1.42
CAS No.9028-48-2
Source
CatalogEXWM-0326
EC No.EC 1.1.1.41
CAS No.9001-58-5
Source
CatalogNATE-1041
EC No.EC 1.1.1.41
CAS No.9001-58-5
SourceE. coli
CatalogNATE-1029
EC No.EC 1.1.1.42
CAS No.9028-48-2
SourceE. coli
CatalogNATE-0351
EC No.EC 1.1.1.42
CAS No.9028-48-2
SourcePichia pastoris
CatalogNATE-0350
EC No.EC 1.1.1.42
CAS No.9028-48-2
SourcePorcine heart
Related Services
Related Protocols
isocitric dehydrogenase -Enzymatic Assay Protocol
Related Reading

Isocitrate dehydrogenase (IDH) is an enzyme that catalyzes the oxidative decarboxylation of isocitrate to produce α-ketoglutarate (α-ketoglutarate) and CO2. This is a two-step process, which involves the oxidation of isocitrate (secondary alcohol) to oxalosuccinate (ketone), and then decarboxylation of the carboxyl group into a ketone to form α-ketoglutarate. In humans, IDH exists in three isoforms: IDH3 catalyzes the third step of the citric acid cycle and at the same time converts NAD+ into NADH in the mitochondria. The isomers IDH1 and IDH2 catalyze the same reaction outside the range of the citric acid cycle and use NADP+ as a cofactor instead of NAD+. They are localized in the cytoplasm as well as mitochondria and peroxisomes.

Protein structure of isocitrate dehydrogenase dimer. Figure 1. Protein structure of isocitrate dehydrogenase dimer.

Clinical significance

Elevated: Acute hepatitis, chronic hepatitis, liver cirrhosis, liver cancer, liver metastatic cancer, cholelithiasis, cholecystitis, bile duct obstruction, pancreatitis, right heart insufficiency, pulmonary infarction, neonatal jaundice, hemolytic disease, etc.

Decrease: Large area of liver cell necrosis.

Factors leading to increased ICD activity: hemolysis, Mn2+, Co2+, Mg2+, aminosalicylic acid, amphotericin B, androgens, anesthetics, carbon tetrachloride, chenodeoxycholic acid, chlorpromazine (chloropromazine) Oxazine), ethanol, isoniazid, methotrexate, butazone.

Factors that cause the decrease of ICD activity: ethylenediaminetetraacetic acid (EDTA), oxalate, sodium chloride, heavy metal ions, fluoride, β-chloromercury benzoic acid, iodoacetate, Ba2+, Zn2+, CN -Wait.

Structure

The NAD-IDH is composed of 3 subunits, is allosterically regulated, and requires an integrated Mg2+ or Mn2+ ion. The closest homologue that has a known structure is the E. coli NADP-dependent IDH, which has only 2 subunits and 13% identity and 29% similarity based on the amino acid sequences, making it dissimilar to human IDH and not suitable for close comparison. All the known NADP-IDHs are homodimers. Most isocitrate dehydrogenases are dimers, to be specific, homodimers (two identical monomer subunits forming one dimeric unit). In comparing C. glutamicum and E. coli, monomer and dimer, respectively, both enzymes were found to "efficiently catalyze identical reactions." However, C. glutamicum was recorded as having ten times as much activity than E. coli and seven times more affinitive/specific for NADP. C. glutamicum favored NADP+ over NAD+.

Active site

In Desulfotalea psychrophila (DpIDH) and porcine (PcIDH) there are three substrates bound to the active site.

Regulation

The IDH step of the citric acid cycle is usually (but not always) an irreversible reaction in the citric acid cycle because it has a large negative free energy change. Therefore, careful adjustments must be made to avoid depletion of isocitrate (and thus avoid the accumulation of α-ketoglutarate). Substrate availability (isocitrate, NAD + or NADP+, Mg2+ / Mn2+), product inhibition (by NADH or NADPH outside the citric acid cycle) and α-ketoglutarate) and competitive feedback inhibition (by the simple mechanism of ATP inhibition stimulates the response).

Reference

  1. Fedoy AE.; et al. Structural and functional properties of isocitrate dehydrogenase from the psychrophilic bacterium Desulfotalea psychrophila reveal a cold-active enzyme with an unusual high thermal stability. J. Mol. Biol. 2007, 372 (1): 130–49.

Sitemap | Privacy Policy | Terms and Conditions
Copyright ©2011 - 2021 Creative Enzymes.
Contact Us 45-1 Ramsey Road, Shirley, NY 11967, USA
Email: info@creative-enzymes.com
Tel: 1-631-562-8517 1-516-512-3133
Fax: 1-631-938-8127
Distributors To view the contact information for a specific location, select the desired country or region: