Guz Jolanta, Oliński Ryszard
Katedra Biochemii Klinicznej, Collegium Medicum im. Ludwika Rydygiera w Bydgoszczy, Uniwersytet Mikołaja Kopernika w Toruniu.
Postepy Hig Med Dosw (Online). 2017 Aug 24;71(1):747-760. doi: 10.5604/01.3001.0010.3853.
Vitamin C (L-ascorbic acid) is a micronutrient best known for its anti-scurvy activity in humans. Vitamin C is involved in many biological processes involving enzymatic reactions that are catalyzed by members of dioxygenases which use Fe(II) and 2-oxoglutarate as a co-substrate.The article reviews recent data that suggest the involvement of ascorbate in dioxygenases catalyzed chromatin and DNA modifications which thereby contribute to epigenetic regulation. Concerning chromatin modification, the dioxygenases are involved in distinct demethylation reactions with varying specificity for the position of the lysine on the target histone. TET hydroxylases catalyse the oxidation of methyl groups in the 5 position of cytosine in DNA yielding 5-hydroxymethylcytosine, while further iterative oxidation reactions results in the formation of 5-formylcytosine and 5-carboxylcytosine. A few previous studies demonstrated that ascorbate may enhance generation of 5-hydroxymethylcytosine in cultured cells, probably acting as a cofactor of TETs during hydroxylation of 5-methylcytosine. Physiological concentrations of ascorbate in human serum (10-100 μM) may guarantee stable level of 5-hydroxymethylcytosine, a modification necessary for epigenetic function of the cell. 5-Hydroxymethylcytosine level is substantially decreased in almost all investigated cancers, what may be linked with cancer development. Therefore, it is possible that supplementation with ascorbate could contribute to better management of individual cancer patient. This issue is also discussed in our paper.
维生素C（L-抗坏血酸）是一种微量营养素，因其对人类的抗坏血病活性而最为人所知。维生素C参与许多生物过程，这些过程涉及由双加氧酶成员催化的酶促反应，双加氧酶使用Fe(II)和2-氧代戊二酸作为共底物。本文综述了最近的数据，这些数据表明抗坏血酸盐参与了双加氧酶催化的染色质和DNA修饰，从而有助于表观遗传调控。关于染色质修饰，双加氧酶参与不同的去甲基化反应，对靶组蛋白上赖氨酸的位置具有不同的特异性。TET羟化酶催化DNA中胞嘧啶5位甲基的氧化，生成5-羟甲基胞嘧啶，而进一步的迭代氧化反应导致5-甲酰基胞嘧啶和5-羧基胞嘧啶的形成。先前的一些研究表明，抗坏血酸盐可能会增强培养细胞中5-羟甲基胞嘧啶的生成，可能在5-甲基胞嘧啶羟化过程中作为TETs的辅助因子。人血清中抗坏血酸盐的生理浓度（10-100μM）可能保证5-羟甲基胞嘧啶的稳定水平，这是细胞表观遗传功能所必需的修饰。在几乎所有研究的癌症中，5-羟甲基胞嘧啶水平都大幅下降，这可能与癌症发展有关。因此，补充抗坏血酸盐有可能有助于更好地管理个体癌症患者。我们的论文也讨论了这个问题。
