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)
| Protein | Definition | Taxonomy |
|---|---|---|
| Isocitrate dehydrogenase [NADP], mitochondrial | An isocitrate dehydrogenase [NADP], mitochondrial that is encoded in the genome of human. [PRO:DNx] | Homo sapiens (human) |
| Isocitrate dehydrogenase [NADP] cytoplasmic | An isocitrate dehydrogenase [NADP] cytoplasmic that is encoded in the genome of human. [PRO:DNx] | Homo sapiens (human) |
Compounds (12)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| ciclopirox | cyclic hydroxamic acid; hydroxypyridone antifungal drug; pyridone | antibacterial agent; antiseborrheic | |
| zuclomiphene | Zuclomiphene: The cis or (Z)-isomer of clomiphene. | stilbenoid | |
| mangostin | alpha-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 a | licochalcone A: has both anti-inflammatory and antineoplastic activities; structure given in first source; isolated from root of Glycyrrhiza inflata; RN given refers to (E)-isomer | chalcones | |
| gamma-mangostin | gamma-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-Mangostin | xanthones | ||
| nsc-287088 | |||
| SYC-435 | SYC-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-5198 | AGI-5198: inhibits isocitrate dehydrogenase 1; structure in first source | ||
| agi-6780 | AGI-6780: inhibits isocitrate dehydrogenases 1 and 2; structure in first source | ||
| ivosidenib | ivosidenib : 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 |
| enasidenib | 1,3,5-triazines; aminopyridine; aromatic amine; organofluorine compound; secondary amino compound; tertiary alcohol | antineoplastic agent; EC 1.1.1.42 (isocitrate dehydrogenase) inhibitor |