Disease relevance of Ogdh

• Cisplatin-induced toxicity is associated with platinum deposition in mouse kidney mitochondria in vivo and with selective inactivation of the alpha-ketoglutarate dehydrogenase complex in LLC-PK1 cells [1].
• Notably, reduced activity of alpha-ketoglutarate dehydrogenase activity has recently been demonstrated in other neurodegenerative diseases, such as Alzheimer, Parkinson, and Huntington diseases [2].
• We previously demonstrated that copper facilitated the formation of reactive oxygen species, and inhibited pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase in vitro and in animal models of Wilson's disease in vivo [3].
• Decreased activities of TCA cycle key enzymes such as isocitrate dehydrogenase (ICDH), succinate dehydrogenase (SDH), malate dehydrogenase (MDH) and alpha-ketoglutarate dehydrogenase (alpha-KGDH) in lung cancer bearing animals were observed [4].

Psychiatry related information on Ogdh

• Abstract alpha-Ketoglutarate dehydrogenase (KGDHC) complex activity is diminished in a number of neurodegenerative disorders and its diminution in Alzheimer Disease (AD) is thought to contribute to the major loss of cerebral energy metabolism that accompanies this disease [5].

High impact information on Ogdh

• In this report a CTL response was generated in BALB/c mice against the ubiquitous self-peptide p2Ca (LSPFPFDL), which binds to Ld and is derived from the mitochondrial enzyme alpha-ketoglutarate dehydrogenase [6].
• Copurified alpha-ketoglutarate dehydrogenase displayed apparent KM values for alpha-ketoglutarate, nicotinamide adenine dinucleotide, and CoA of 1.25 mM, 67 muM, and 50 muM, respectively [7].
• Pyruvate dehydrogenase, but not alpha-ketoglutarate dehydrogenase, was inactivated specifically by adenosine triphosphate with concomitant phosphorylation, and it was reactivated at 10 mM Mg2+ by a protein fraction separated from the complex during purification [7].
• In purified enzymes, glutaryl-CoA but not glutaric or 3-hydroxyglutaric induced an uncompetitive inhibition of alpha-ketoglutarate dehydrogenase complex activity [2].
• In contrast to alpha-ketoglutarate dehydrogenase complex, no direct inhibition of glutaryl-CoA, glutaric acid, and 3-hydroxyglutaric acid was found in other enzymes tested [2].

Biological context of Ogdh

• It is surprising that the inhibition of cytochrome oxidase also diminished the activity of the alpha-ketoglutarate dehydrogenase complex (KGDHC), a Krebs cycle enzyme [8].
• Here we demonstrated that these toxic exposures were accompanied by an early marked reduction in both pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase activities, followed by a decrease in neuronal mitochondrial transmembrane potential and ATP, prior to murine cortical neuronal death [3].

Anatomical context of Ogdh

• High mRNA levels of d1401/Ogdh were observed in the olfactory bulb, hippocampus, cerebellum, and pons, whereas those of d1501 were detected in the granule cells of the olfactory bulb, dentate gyrus, and cerebellum [9].
• The activity levels of a key mitochondrial enzyme, alpha-ketoglutarate dehydrogenase complex (KGDHC), were uniquely distributed among different cell types: The highest activity was in the endothelial cells, and the lowest was in primary microglia and neurons [10].
• Quantitative alpha-ketoglutarate dehydrogenase activity staining in brain sections and in cultured cells [11].
• Very long chain acyl coenzyme A dehydrogenase and alpha-ketoglutarate dehydrogenase activities were unaffected during aging in both heart and skeletal muscle [12].
• While glutamate dehydrogenase and alpha-ketoglutarate dehydrogenase complex activities are lower in the cerebellum and brain stem of the CD mouse, alanine aminotransferase and succinate semialdehyde dehydrogenase (SSADH) activities and succinate level are similar to the levels observed in the wild type [13].

Associations of Ogdh with chemical compounds

• Isolated mitochondrial alpha-ketoglutarate dehydrogenase (KGDHC) and pyruvate dehydrogenase (PDHC) complexes produced superoxide and H(2)O(2) [14].
• Treatment with 50 or 100 microM cisplatin for 3 h, followed by removal of cisplatin from the medium for 24 h, resulted in a pronounced loss of alpha-ketoglutarate dehydrogenase complex (KGDHC) activity in both mitAspAT-transfected cells and control cells [1].
• Sequence analysis revealed that d1401 and c1502 were derivatives of Ogdh (oxoglutarate dehydrogenase) and QP-C (ubiquinol-cytochrome c reductase complex ubiquinone-binding protein), respectively [9].
• Inhibition of the alpha-ketoglutarate dehydrogenase complex by the myeloperoxidase products, hypochlorous acid and mono-N-chloramine [5].
• Inhibition of mitochondrial alpha-ketoglutarate dehydrogenase by 1-methyl-4-phenylpyridinium ion [15].

Other interactions of Ogdh

• Moreover, b1402 and d1501 were identified as transcripts of a predicted gene (4933409K07Rik) and a novel EST, respectively. b1402 and d1501 were abundantly present in the cerebellum, whereas c1502/QP-C and d1401/Ogdh were widely distributed in various mouse tissues [9].

References