

Myo肌醇与D-手性肌醇有何关系

肌醇最早被发现是从肌肉中提取的一种六羟基环己烷化合物,属于神经醇家族,有九种不同的异构体。维生素B8通常指肌醇,实际上它并不是真正意义上的维生素。
肌醇在体内的作用非常广泛,它在构建细胞膜的过程中是必不可少的,也是中枢神经系统中的“第二信使”。肌醇还有很多其他的用途,包括提高生育能力(如用于治疗PCOS,提高精子质量)[1-2];葡萄糖和脂质代谢(改善胰岛素抵抗)[3-5];肌醇还有助于甲状腺功能[6-7];神经系统疾病和新生儿呼吸功能[8-9],还有一些研究发现,肌醇可能对癌症治疗是有益的[10-15]。
肌醇最常见的两种形式是Myo肌醇和D-手性肌醇,Myo肌醇相对来说比较容易从饮食中获得,而D-手性肌醇只有在少数食物中才有,人体内的D-手性肌醇主要是由Myo肌醇合成的。
Myo肌醇的产生途径,一条是从食物中外源性获得,另一条途径就是通过葡萄糖-6-磷酸(Glu6p)内源性合成。Myo肌醇可以进行差向异构化,生成D-手性肌醇(DCI)。Myo-Ins还可以构成了几种衍生的肌醇磷酸盐 (InsPs)、复杂的大分子。
在人体中,InsP最初是从磷酸肌醇(PI)的水解中获得的,因此,肌醇细胞内代谢的关键转折点是PIP2水解释放甘油二酯(DAG)和三磷酸肌醇(InsP3)。InsP3是关键的第二信使,通过与特异性InsP3受体结合,诱导钙从内质网中释放出来。
细胞中主要是Myo肌醇,Myo肌醇也可以通过差向异构酶转化为D-手性肌醇,在胰岛素抵抗的情况下,差向异构化过程受到抑制,会导致Myo肌醇和D-手性肌醇之间的比例增加。
肌醇的这种不可逆反应经过微调,会导致不同组织中两种异构体的浓度非常不同。在血浆中,Myo肌醇和手性肌醇之间的比例为40:1,能量依赖组织,如脂肪或肝脏中,这一比例下降到2:1。相比之下,葡萄糖消耗率比较高的组织,如大脑中,这个比例为200:1。
胰岛素抵抗的情况下,差向异构化过程受到抑制,Myo肌醇和D-手性肌醇之间的比例增加,但这种情况不会发生在卵巢当中,这就是所谓的卵巢悖论。IR不会发生在卵巢中,卵巢组织对胰岛素仍然敏感,并且仍然对大量循环胰岛素敏感,这是全身IR的结果。高胰岛素血症导致卵巢过度刺激,导致特异性差向异构酶增加,随后卵巢组织手性肌醇水平增加,在健康女性的卵泡液中,Myo肌醇和手性肌醇之间的比例为100:1,IR的女性,这个比例会下降到0.2:1。Myo肌醇耗竭会导致促卵泡激素信号传导和卵母细胞质量下降,导致PCOS的发生。
使用肌醇治疗,通常是为了恢复体内肌醇的正常比例,比如需要将血浆比例恢复到40:1,胰岛素抵抗的多囊女性使用肌醇治疗,是为了提高Myo肌醇的比例,满足生理上的需求。
[1] Facchinetti F, Orrù B, Grandi G, Unfer V. Short-term effects of metformin and myo-inositol in women with Polycystic Ovarian Syndrome (PCOS): a meta-analysis of randomized clinical trials. Gynecol Endocrinol. 2019;35(3):198–206.
[2] Fatima K, Jamil Z, Faheem S, Adnan A, Javaid SS, Naeem H, et al. Effects of myo-inositol vs. metformin on hormonal and metabolic parameters in women with PCOS: a meta-analysis. Ir J Med Sci. 2023;192:2801–8.
[3] Motuhifonua SK, Lin L, Alsweiler J, Crawford TJ, Crowther CA. Antenatal dietary supplementation with myo-inositol for preventing gestational diabetes. Cochrane Database Syst Rev. 2023 Feb 15;2(2):CD011507. doi: 10.1002/14651858.CD011507.pub3. PMID: 36790138; PMCID: PMC9930614.
[4] Mashayekh-Amiri S, Mohammad-Alizadeh-Charandabi S, Abdolalipour S, Mirghafourvand M. Myo-inositol supplementation for prevention of gestational diabetes mellitus in overweight and obese pregnant women: a systematic review and meta-analysis. Diabetol Metab Syndr. 2022 Jul 6;14(1):93. doi: 10.1186/s13098-022-00862-5. PMID: 35794663; PMCID: PMC9258131.
[5] Wei J, Yan J, Yang H. Inositol Nutritional Supplementation for the Prevention of Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Nutrients. 2022 Jul 9;14(14):2831. doi: 10.3390/nu14142831. PMID: 35889788; PMCID: PMC9318937.
[6] Piras C, Pibiri M, Leoni VP, Balsamo A, Tronci L, Arisci N, et al. Analysis of Metabolomics Profile in Hypothyroid Patients Before and After Thyroid Hormone Replacement. J Endocrinol Invest (2020). 10.1007/s40618-020-01434-y
[7] Barbaro D, Orrù B, Unfer V. Iodine and Myo-Inositol: A Novel Promising Combination for Iodine Deficiency. Front Endocrinol (2019) 10:457. 10.3389/fendo.2019.0045710
[8] Concerto C, Chiarenza C, Di Francesco A, Natale A, Privitera I, Rodolico A, Trovato A, Aguglia A, Fisicaro F, Pennisi M, Bella R, Petralia A, Signorelli MS, Lanza G. Neurobiology and Applications of Inositol in Psychiatry: A Narrative Review. Curr Issues Mol Biol. 2023 Feb 20;45(2):1762-1778. doi: 10.3390/cimb45020113. PMID: 36826058; PMCID: PMC9955821.
[9] Gianfranco C., Vittorio U., Silvia B., Francesco D. Myo-inositol in the treatment of premenstrual dysphoric disorder. Hum. Psychopharmacol. 2011;26:526–530. doi: 10.1002/hup.1241.
[10] Arrest and Apoptotic Death of Androgen-Dependent Human Prostate Carcinoma Lncap Cells. Neoplasia. 2004;6:646–659. doi: 10.1593/neo.04232.
[11] Deliliers G.L., Servida F., Fracchiolla N.S., Ricci C., Borsotti C., Colombo G., Soligo D. Effect of Inositol Hexaphosphate (Ip(6)) on Human Normal and Leukaemic Haematopoietic Cells. Br. J. Haematol. 2002;117:577–587. doi: 10.1046/j.1365-2141.2002.03453.x.
[12] Vucenik I., Shamsuddin A.M. Protection against Cancer by Dietary Ip6 and Inositol. Nutr. Cancer. 2006;55:109–125. doi: 10.1207/s15327914nc5502_1.
[13] Vucenik I., Passaniti A., Vitolo M.I., Tantivejkul K., Eggleton P., Shamsuddin A.M. Anti-Angiogenic Activity of Inositol Hexaphosphate (Ip6) Carcinogenesis. 2004;25:2115–2123. doi: 10.1093/carcin/bgh232.
[14] Graf E., Eaton J.W. Antioxidant Functions of Phytic Acid. Free Radic. Biol. Med. 1990;8:61–69. doi: 10.1016/0891-5849(90)90146-A.
[15] Weglarz L., Molin I., Orchel A., Parfiniewicz B., Dzierzewicz Z. Quantitative Analysis of the Level of P53 and P21(Waf1) Mrna in Human Colon Cancer Ht-29 Cells Treated with Inositol Hexaphosphate. Acta Biochim. Pol. 2006;53:349–356. doi: 10.18388/abp.2006_3348.