isocitrate metabolic process
Definition
Target type: biologicalprocess
The chemical reactions and pathways involving isocitrate, the anion of isocitric acid, 1-hydroxy-1,2,3-propanetricarboxylic acid. Isocitrate is an important intermediate in the TCA cycle and the glycoxylate cycle. [ISBN:0198506732]
Isocitrate metabolism is a crucial step in the citric acid cycle (Krebs cycle), a central metabolic pathway that generates energy in the form of ATP through the oxidation of carbohydrates, fats, and proteins. It involves the conversion of isocitrate to α-ketoglutarate, a key intermediate in the cycle. This process is catalyzed by the enzyme isocitrate dehydrogenase (IDH), which exists in two main forms: IDH1 and IDH2. Both enzymes require NAD+ as an electron acceptor and use it to oxidize the secondary alcohol group of isocitrate to a ketone group, yielding α-ketoglutarate. However, they differ in their localization and cofactor requirements. IDH1 is located in the cytoplasm and uses NADP+ as a cofactor, while IDH2 resides in the mitochondria and utilizes NAD+ as a cofactor.
The reaction catalyzed by IDH is a decarboxylation, meaning that it involves the release of carbon dioxide (CO2) from isocitrate. This decarboxylation step is highly regulated and is influenced by factors such as the availability of substrates (isocitrate and NAD+), the presence of inhibitors, and the cellular energy state.
The importance of isocitrate metabolism lies in its role in energy production, but it also contributes to the biosynthesis of various essential molecules, including amino acids, fatty acids, and heme. Additionally, isocitrate metabolism is linked to other metabolic pathways, such as the glyoxylate cycle, which allows organisms to utilize two-carbon compounds like acetate as a carbon source.
In summary, isocitrate metabolism is a vital process that plays a crucial role in cellular energy production and the biosynthesis of essential molecules. It involves the conversion of isocitrate to α-ketoglutarate via the enzyme IDH, with the release of CO2 as a byproduct. This process is tightly regulated and is influenced by several factors, highlighting its importance in maintaining cellular homeostasis.'
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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 |