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isocitrate dehydrogenase (NADP+) activity

Definition

Target type: molecularfunction

Catalysis of the reaction: isocitrate + NADP+ = 2-oxoglutarate + CO2 + NADPH. [RHEA:19629]

Isocitrate dehydrogenase (NADP+) is an enzyme that catalyzes the oxidative decarboxylation of isocitrate to α-ketoglutarate, utilizing NADP+ as an electron acceptor. This reaction is a key step in the citric acid cycle, also known as the Krebs cycle, a central metabolic pathway that generates energy in the form of ATP. The enzyme's primary molecular function involves several crucial steps:

1. **Substrate Binding:** Isocitrate dehydrogenase (NADP+) binds to its substrate, isocitrate, and the cofactor NADP+.
2. **Oxidation and Decarboxylation:** The enzyme oxidizes the secondary alcohol group of isocitrate to a ketone group, simultaneously releasing a molecule of carbon dioxide (CO2). This process is facilitated by the enzyme's active site, which contains a metal ion, usually manganese (Mn2+), that assists in the oxidation reaction.
3. **NADP+ Reduction:** The electrons removed from isocitrate are transferred to NADP+, reducing it to NADPH. NADPH is an important reducing agent in various metabolic pathways, including fatty acid biosynthesis and the detoxification of reactive oxygen species.
4. **Product Release:** The enzyme releases the product, α-ketoglutarate, and the reduced cofactor, NADPH.

The isocitrate dehydrogenase (NADP+) activity is essential for the proper functioning of the citric acid cycle, and its deficiency can lead to various metabolic disorders.'
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Proteins (2)

ProteinDefinitionTaxonomy
Isocitrate dehydrogenase [NADP], mitochondrialAn isocitrate dehydrogenase [NADP], mitochondrial that is encoded in the genome of human. [PRO:DNx]Homo sapiens (human)
Isocitrate dehydrogenase [NADP] cytoplasmicAn isocitrate dehydrogenase [NADP] cytoplasmic that is encoded in the genome of human. [PRO:DNx]Homo sapiens (human)

Compounds (12)

CompoundDefinitionClassesRoles
ciclopiroxcyclic hydroxamic acid;
hydroxypyridone antifungal drug;
pyridone
antibacterial agent;
antiseborrheic
zuclomipheneZuclomiphene: The cis or (Z)-isomer of clomiphene.stilbenoid
mangostinalpha-mangostin : A member of the class of xanthones that is 9H-xanthene substituted by hydroxy group at positions 1, 3 and 6, a methoxy group at position 7, an oxo group at position 9 and prenyl groups at positions 2 and 8. Isolated from the stems of Cratoxylum cochinchinense, it exhibits antioxidant, antimicrobial and antitumour activities.

mangostin: xanthone from rind of Garcinia mangostana Linn. fruit
aromatic ether;
phenols;
xanthones
antimicrobial agent;
antineoplastic agent;
antioxidant;
plant metabolite
licochalcone alicochalcone A: has both anti-inflammatory and antineoplastic activities; structure given in first source; isolated from root of Glycyrrhiza inflata; RN given refers to (E)-isomerchalcones
gamma-mangostingamma-mangostin : A member of the class of xanthones that is 9H-xanthene substituted by hydroxy group at positions 1, 3, 6 and 7, an oxo group at position 9 and prenyl groups at positions 2 and 8. Isolated from the stems of Cratoxylum cochinchinense, it exhibits antitumour activity.phenols;
xanthones
antineoplastic agent;
plant metabolite;
protein kinase inhibitor
beta-Mangostinxanthones
nsc-287088
SYC-435SYC-435 : A cyclic hydroxamic acid that is 1-hydroxypyridin-2(1H)-one in which the hydrogens at positions 4 and 6 are substituted by methyl and benzyl groups, respectively. It is a potent inhibitor of mutant isocitrate dehydrogenase 1 (Ki values of 190 nM against R132H mutant and 120 nM against R132C mutant).benzenes;
cyclic hydroxamic acid;
pyridone
antineoplastic agent;
EC 1.1.1.42 (isocitrate dehydrogenase) inhibitor
agi-5198AGI-5198: inhibits isocitrate dehydrogenase 1; structure in first source
agi-6780AGI-6780: inhibits isocitrate dehydrogenases 1 and 2; structure in first source
ivosidenibivosidenib : A tertiary carboxamide resulting from the formal condensation of the carboxy group of (2S)-1-(4-cyanopyridin-2-yl)-5-oxopyrrolidine-2-carboxylic acid with the secondary amino group of (2S)-2-(2-chlorophenyl)-N-(3,3-difluorocyclobutyl)-2-[(5-fluoropyridin-3-yl)amino]acetamide. It is approved by the FDA for the treatment of acute myeloid leukemia (AML) in patients with an isocitrate dehydrogenase-1 (IDH1) mutation.

ivosidenib: an inhibitor of isocitrate dehydrogenase 1 (IDH1) for treatment of acute myeloid leukemia (AML)
cyanopyridine;
monochlorobenzenes;
organofluorine compound;
pyrrolidin-2-ones;
secondary carboxamide;
tertiary carboxamide
antineoplastic agent;
EC 1.1.1.42 (isocitrate dehydrogenase) inhibitor
enasidenib1,3,5-triazines;
aminopyridine;
aromatic amine;
organofluorine compound;
secondary amino compound;
tertiary alcohol
antineoplastic agent;
EC 1.1.1.42 (isocitrate dehydrogenase) inhibitor