同型半胱氨酸(HCY)水平增高是慢性血管疾病的独立危险因子,但HCY的来源不是从食物中吸取,其由蛋氨酸在甲基(CH
3)循环代谢的中间产物。甲基化代谢亢进,再甲基化或转硫化代谢酶基因突变或功能障碍等原因均可造成甲基循环代谢失衡,从而导致HCY推积,患者出现高同型半胱氨酸血症(HHCY),动脉硬化等为特征的临床症状和体征。胱硫醚β-合酶(CBS)基因可将HCY转硫化成为胱硫醚,后者再经过胱硫醚-γ-裂解酶(CTH)裂解成丙酮酸、硫酸和水,达到有效降低HCY水平,降低动脉硬化进展,保障机体健康。本文综述近年来HCY代谢通路及其与心血管疾病的关系等的研究许多新进展。
Elevated homocysteine (HCY) level is an independent risk factor for chronic vascular diseases, but HCY is not derived from food and is an intermediate product of methionine cyclic metabolism in methyl (CH
3). Hypermethylation metabolism, gene mutation of demethylation or trans-sulfuration metabolizing enzyme or dysfunction and other reasons can all cause imbalance of methyl circulation metabolism, thus causing HCY accumulation, patients with clinical symptoms and signs characterized by hyperhomocysteinemia (HHCY) and arteriosclerosis. Cystathionine β-synthase (CBS) gene can convert HCY into cystathionine, which is then cleaved into pyruvic acid, sulfuric acid and water by cystathionine-γ-lyase (CTH) to effectively reduce HCY level, reduce arteriosclerosis pro- gress and ensure body health. In recent years, there are many new advances in HCY metabolic pathway and its relationship with cardiovascular diseases. This article reviews them.
CBS T833C位点的突变使其编码的异亮氨酸代替了苏氨酸,导致酶蛋白分子中磷酸吡哆醛(PLP)结合位点的构像变化,从而影响CBS与PLP结合。G919A突变使甘氨酸代替了丝氨酸,影响CBS的活性;第4外显子中的碱基丢失引起CBS活性完全丧失。胱硫醚β-合酶基因T833C,G919A位点突变均可导致血浆同型半胱氨酸浓度明显增高;胱硫醚β-合酶基因G919A和T833C基因突变与青年脑血管病发病无直接相关性。CBS844ins68突变可能不足以构成2型糖尿病的独立遗传性危险因子 [27]。
农 茜,陆文权,梁 烨,赖腾芳,李天资. 同型半胱氨酸与甲基代谢及其胱硫醚酶基因研究进展Advances in Homocysteine, Methyl Metabolism and Cystathionidase Gene[J]. 临床医学进展, 2020, 10(07): 1277-1284. https://doi.org/10.12677/ACM.2020.107194
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