Target type: biologicalprocess
A modification of the TCA cycle occurring in some plants and microorganisms, in which isocitrate is cleaved to glyoxylate and succinate. Glyoxylate can then react with acetyl-CoA to form malate. [ISBN:0198506732]
The glyoxylate cycle is a metabolic pathway that occurs in plants, bacteria, fungi, and some protists. It is a variation of the citric acid cycle that allows these organisms to grow on two-carbon compounds, such as acetate, as their sole source of carbon. The key difference between the glyoxylate cycle and the citric acid cycle is the presence of two unique enzymes, isocitrate lyase and malate synthase.
The glyoxylate cycle begins with the entry of acetyl-CoA into the cycle, which is derived from the breakdown of fatty acids or other two-carbon compounds. The acetyl-CoA condenses with oxaloacetate to form citrate, just as in the citric acid cycle. However, instead of being decarboxylated to α-ketoglutarate, isocitrate is cleaved by isocitrate lyase into glyoxylate and succinate. Glyoxylate then reacts with acetyl-CoA in a reaction catalyzed by malate synthase to form malate. Malate can then enter the citric acid cycle, be converted to pyruvate for gluconeogenesis, or be used for other metabolic processes.
The glyoxylate cycle allows organisms to bypass the decarboxylation steps of the citric acid cycle, thus conserving carbon. This is particularly important for organisms growing on two-carbon compounds because they cannot directly generate four-carbon intermediates for the citric acid cycle. The glyoxylate cycle also allows for the net synthesis of carbohydrates from acetyl-CoA, which is essential for growth and development in organisms that cannot fix carbon dioxide through photosynthesis.
The glyoxylate cycle plays a crucial role in the survival and growth of organisms in a variety of environments. For example, it is essential for the growth of plants on acetate, which is a major component of their root exudates. It is also important for the metabolism of fatty acids in mammals, where it allows for the conversion of acetyl-CoA from fatty acid breakdown into glucose. Furthermore, the glyoxylate cycle is involved in the detoxification of toxic compounds in some organisms.'
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| 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) |
| 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 |