Piruvat karboksilaza fermentining farmakologik roli: Metabolik kasalliklar va onkologiyada terapevtik nishon sifatidagi klinik-biokimyoviy tahlili.
Keywords:
Piruvat karboksilaza, farmakologik nishon, glyukoneogenez, ferment ingibitorlari, metabolik sindrom, onkologiya, anapleroz, gepatotsitlar.Abstract
Piruvat karboksilaza (PK) glikoliz va glyukoneogenez yo'llarini o'zaro bog'lab, piruvatning oksaloatsetatga ATP ga bog'liq karboksillanishini boshqaruvchi hal qiluvchi anaplerotik ferment sifatida faoliyat yuritadi. PK faolligining patologik ortishi 2-tip qandli diabetda jigarda glyukoza ishlab chiqarilishining tezlashishi hamda qattiq o'smalarda kuzatiladigan metabolik qayta dasturlash bilan bevosita bog'liq. Mazkur tadqiqot PK ning asosiy terapevtik nishon sifatidagi farmakologik ahamiyatini baholaydi va metabolik buzilishlarni yumshatishda yangi allosterik ingibitorlarning dozaga bog'liq samaradorligini tahlil qiladi. In vitro enzimologik tahlillar va in vivo hayvonlar modellari (dietaga bog'liq semizlik — DIO) usullaridan foydalangan holda, PK va eksperimental farmakologik vositalar o'rtasidagi o'zaro ta'sir dinamikasi miqdoriy jihatdan o'rganildi. Empirik ma'lumotlar shuni ko'rsatadiki, PK ning biotin-karboksilaza domenini maqsadli ingibirlash tizimli laktat atsidozni keltirib chiqarmasdan, patologik glyukoneogenezni qariyb 42% ga sezilarli darajada pasaytiradi. Qayd etilgan termodinamik bog'lanish profillari va farmakokinetik modellar selektiv PK modulyatorlari patologik lipogenez va o'sma proliferatsiyasi tarmoqlarini samarali ravishda uzib qo'yishi mumkinligini isbotlaydi. Olingan natijalar dinamikasi farmatsevtika sanoatida yangi avlod antidiabetik va antineoplastik dori vositalarini sintez qilish uchun molekulyar baza yaratadi. Bu esa piruvat karboksilazani shunchaki oraliq metabolik vositachi emas, balki ilg'or farmakologik aralashuv uchun markaziy biokimyoviy tugun sifatida namoyon qiladi.
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