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[资源] 同型半胱氨酸血症 Homocysteinemia

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发表于 2019-2-16 00:01:08 | 显示全部楼层 |阅读模式


同型半胱氨酸/ˌhoʊmoʊsɪstiːn/是一种非蛋白原性α-氨基酸。它是氨基酸半胱氨酸的同源物,不同之处在于另外的亚甲基桥(-CH2-)。它通过去除其末端Cε甲基从甲硫氨酸生物合成。同型半胱氨酸可以通过某些B族维生素再循环到蛋氨酸中或转化为半胱氨酸。

血液中高水平的高半胱氨酸(高同型半胱氨酸血症)使人更容易发生内皮细胞损伤,导致血管炎症,进而可能导致动脉粥样硬化,从而导致缺血性损伤。[3]因此,高同型半胱氨酸血症是冠状动脉疾病的可能危险因素。当动脉粥样硬化斑块阻断血流到冠状动脉时会发生冠状动脉疾病,冠状动脉为心脏提供含氧血液。

高同型半胱氨酸血症与血栓,心脏病发作和中风的发生有关,但尚不清楚高同型半胱氨酸血症是否是这些病症的独立危险因素。[引证需要]高同型半胱氨酸血症也与早期妊娠丢失有关[4]和神经管缺陷。[5]

目录
1 结构
2 生物合成和生化作用
2.1 半胱氨酸的生物合成
2.2 蛋氨酸回收
2.3 其他生化反应的反应
3 同型半胱氨酸水平
4 升高的高半胱氨酸
5 参考

结构


两性离子形式的(S) - 同型半胱氨酸(左)和(R) - 同型半胱氨酸(右)
同型半胱氨酸在中性pH值下作为两性离子存在。

生物合成和生化作用


两种同型半胱氨酸的主要生化作用。 (在图像的左中间可以看到同型半胱氨酸。)它可以从甲硫氨酸合成,然后通过SAM循环转换回蛋氨酸或用于产生半胱氨酸和α-酮丁酸。
同源半胱氨酸不是从饮食中获得的。[6]相反,它通过多步骤过程从甲硫氨酸生物合成。首先,甲硫氨酸从ATP接受腺苷基团,由S-腺苷甲硫氨酸合成酶催化的反应,得到S-腺苷甲硫氨酸(SAM)。然后SAM将甲基转移至受体分子(例如,在肾上腺素合成期间去甲肾上腺素作为受体,DNA甲基转移酶作为DNA甲基化过程中的中间受体)。然后将腺苷水解,得到L-高半胱氨酸。 L-同型半胱氨酸有两个主要的命运:通过四氢叶酸(THF)转化回L-蛋氨酸或转化为L-半胱氨酸。[7]

半胱氨酸的生物合成
哺乳动物通过高半胱氨酸生物合成氨基酸半胱氨酸。胱硫醚β-合酶催化高半胱氨酸和丝氨酸的缩合,得到胱硫醚。该反应使用吡哆醇(维生素B6)作为辅助因子。然后胱硫醚γ-裂解酶将该双氨基酸转化为半胱氨酸,氨和α-酮丁酸。细菌和植物依赖于不同途径产生半胱氨酸,依赖于O-乙酰丝氨酸。[8]


MTHFR代谢:叶酸循环,蛋氨酸循环,反式硫化和高同型半胱氨酸血症。 5-MTHF:5-甲基四氢叶酸; 5,10甲基四氢叶酸; BAX:Bcl-2相关X蛋白; BHMT:甜菜碱 - 高半胱氨酸S-甲基转移酶; CBS:胱硫醚β合成酶; CGL:胱硫醚γ-裂解酶; DHF:二氢叶酸(维生素B9); DMG:二甲基甘氨酸; dTMP:苷一磷酸; dUMP:脱氧尿苷一磷酸; FAD +黄素腺嘌呤二核苷酸; FTHF:10-甲酰基四氢叶酸; MS:蛋氨酸合成酶; MTHFR:甲基四氢叶酸酯还原酶; SAH:S-腺苷-L-高半胱氨酸;相同:S-腺苷-L-蛋氨酸; THF:四氢叶酸。
蛋氨酸打捞
同型半胱氨酸可以再循环到蛋氨酸中。该方法使用N5-甲基四氢叶酸盐作为甲基供体和钴胺素(维生素B12)相关的酶。关于这些酶的更多细节可以在关于蛋氨酸合酶的文章中找到。

其他生化反应的反应
同型半胱氨酸可环化得到高半胱氨酸硫代内酯,一种五元杂环。由于这种“自我循环”反应,含有高半胱氨酸的肽倾向于通过产生氧化应激的反应裂解自己。[9]

同型半胱氨酸还可作为多巴胺D2受体的变构拮抗剂。[10]有人提出,同型半胱氨酸及其硫代内酯可能在早期地球的生命出现中发挥了重要作用。[11]

同型半胱氨酸水平


总血浆同型半胱氨酸
男性的同型半胱氨酸水平通常高于女性,并且随着年龄的增长而增加。[12] [13]

西方人群的常见水平为10至12μmol/ L,在B族维生素摄入量较低的人群或老年人(如鹿特丹,弗雷明汉)中发现20μmol/ L的水平[14] [15]。

同型半胱氨酸的血液参考范围:

以上范围仅作为示例提供; 应始终使用产生结果的实验室提供的范围来解释测试结果。

升高的同型半胱氨酸
主要文章:高同型半胱氨酸血症
血清中异常高半胱氨酸水平异常高于15μmol/ L,是一种称为高同型半胱氨酸血症的医学病症[19]。 据称这是发生多种疾病的重要危险因素,包括血栓形成,[20]神经精神疾病,[21] [22] [23] [24]和骨折[25] [26]。 它还被发现与微量白蛋白尿有关,微量白蛋白尿是未来心血管疾病和肾功能不全的风险的有力指标。[27]

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