Table 5.
Mitochondria Disorders – TCA Cycle.
| Enzymes | Role | Disease Name | Upregulated Cancers | Downregulated Cancers |
|---|---|---|---|---|
| Citrate synthase (CS) | Binds with the oxaloacetate and reacts with acetyl-CoA, leading to the production of citrate. | Ovarian (226), pancreas (227), and colon (228). | Cervical (229). | |
| Aconitase (ACO2) | Catalyzes the conversion of citrate into isocitrate | Cerebellar-retinal degeneration (230, 231) and with severe optic atrophy and spastic paraplegia (232). | HCC (233). | Gastric cancer (234) and colorectal cancer (235). |
| Isocitrate dehydrogenase (IDH). Three IDH isoforms exist IDH1, IDH2, and IDH3. | Converts of isocitrate into α-ketoglutarate (α-KG) | IDH1 and IDH2 in glioblastoma (236) IDH2 in colorectal (237) and lung (238). IDH3-a in glioblastoma (239) and in HCC (240). | ||
| α-ketoglutarate dehydrogenase (α-KGDH), also called 2-oxoglutarate dehydrogenase (OGDH). | Converts α-KG into succinyl-CoA | alpha-ketoglutarate dehydrogenase complex (KGDHC) deficiency | Gastric (241). | |
| Succinyl-CoA synthetase (SCS), also known as Succinyl-CoA ligase. SCS is composed of two subunits, an α-subunit which is encoded by the gene SUCLG1, and the β-subunit which is encoded by the gene SUCLA2 (specificity for ADP), or by the gene SUCLG2 (specificity for GDP). |
Breaks down succinyl-CoA into succinate and free CoA, and converts ADP or GDP into ATP or GTP, respectively. | Succinyl-CoA ligase deficiency | SUCLG1 in acute myeloid leukemia (242). | SUCLA2 in prostate (243). |
| Succinate dehydrogenase (SDH), also known as Succinate-coenzyme Q reductase (SQR). SDH is composed of four subunits, SDHA, SDHB, SDHC and SDHD. | Catalyzes the oxidation of succinate to fumarate and transfers electrons from succinate to ubiquinone (coenzyme Q). | Succinate dehydrogenase (SDH) deficiency | SDHB in ovarian (244). | |
| Fumarase, also known as fumarate hydratase | Catalyzes the hydration of fumarate into L-malate. | Fumarase deficiency, also known as Fumarate hydratase deficiency or Fumaric aciduria. | Clear cell renal carcinomas (245). | |
| Malate dehydrogenase (MDH2) | Catalyzes the reversible conversion of malate into oxaloacetate | Mitochondrial malate dehydrogenase (MDH2) deficiency | Prostate (246). |