Zogulitsa

Pa 70% ya ma glioma otsika amakhala ndi kusintha kwa heterozygous R132H mu jini yolembera isocitrate dehydrogenase 1 (IDH1).Izi zimapereka puloteniyo ndi kuthekera kwatsopano kosinthira α-ketoglutarate kukhala 2-hydroxyglutarate, zomwe zimatsogolera ku tumorigenesis.Gwero lalikulu la kupanga 2-hydroxyglutarate ndi glutamine, yomwe, mu khansa, imakhalanso gwero la tricarboxylic acid cycle (TCA) anaplerosis.Njira ina ya anaplerosis ndi pyruvate flux kudzera pa pyruvate carboxylase (PC), yomwe ndi njira yodziwika bwino mu astrocyte wamba.Cholinga cha phunziroli chinali kudziwa ngati PC imakhala ngati gwero la TCA anaplerosis mu maselo osinthika a IDH1 momwe glutamine imagwiritsidwa ntchito pakupanga 2-hydroxyglutarate.Kuthamanga kwa pyruvate kudzera pa PC komanso kudzera pa pyruvate dehydrogenase (PDH) kunadziwika pogwiritsa ntchito maginito a resonance spectroscopy kuti afufuze zolemba za [2-¹³C] zochokera ku glucose ¹³C-labe led glutamate ndi glutamine.Mayesero a zochitika, RT-PCR ndi kuzunguliridwa kwa kumadzulo kunagwiritsidwa ntchito kufufuza mawu ndi zochitika za michere yoyenera.Deta ya Cancer Genome Atlas (TCGA) idafufuzidwa kuti iwonetsere ma enzymes mu zitsanzo za glioma yaumunthu.Poyerekeza ndi maselo amtundu wa nyama zakutchire, maselo a mutant IDH1 amachulukitsa kwambiri kuthamanga kwapakati kudzera pa PC.Izi zinagwirizanitsidwa ndi kuwonjezeka kwakukulu kwa ntchito za PC ndi kufotokozera.Panthawi imodzimodziyo, ntchito ya PDH inachepa kwambiri, mwinamwake imakhala yosakanikirana ndi kuwonjezeka kwakukulu koletsa PDH phosphorylation ndi PDH kinase 3. Mogwirizana ndi kuwonetsetsa m'maselo, kusanthula deta ya TCGA kunasonyeza kuwonjezeka kwakukulu kwa PC kufotokoza mu mutant IDH-kufotokoza zitsanzo za glioma zaumunthu poyerekeza ndi zakutchire- lembani IDH. Zomwe tapeza zikusonyeza kuti kusintha kwa PC ndi PDH kungakhale gawo lofunika kwambiri la kusintha kwa ma cell ku kusintha kwa IDH1 ndipo kungakhale ngati zolinga zothandizira.