Human choline dehydrogenase (CHD) is located in the inner membrane of mitochondria primarily in liver and kidney and catalyzes the oxidation of choline to glycine betaine. Its physiological role is to regulate the concentrations of choline and glycine betaine in the blood and cells. Choline is important for regulation of gene expression, the biosynthesis of lipoproteins and membrane phospholipids and for the biosynthesis of the neurotransmitter acetylcholine; glycine betaine plays important roles as a primary intracellular osmoprotectant and as methyl donor for the biosynthesis of methionine from homocysteine, a required step for the synthesis of the ubiquitous methyl donor S-adenosyl methionine. Recently, CHD has generated considerable medical attention due to its association with various human pathologies, including male infertility, homocysteinuria, breast cancer and metabolic syndrome. Despite the renewed interest, the biochemical characterization of the enzyme has lagged behind due to difficulties in the obtainment of purified, active and stable enzyme. This review article summarizes the medical relevance and the physiological roles of human CHD, highlights the biochemical knowledge on the enzyme, and provides an analysis based on the comparison of the protein sequence with that of bacterial choline oxidase, for which structural and biochemical information is available.

译文

人胆碱脱氢酶(CHD)位于线粒体内膜中,主要位于肝脏和肾脏中,并催化胆碱氧化为甘氨酸甜菜碱。它的生理作用是调节血液和细胞中胆碱和甘氨酸甜菜碱的浓度。胆碱对调节基因表达,脂蛋​​白和膜磷脂的生物合成以及神经递质乙酰胆碱的生物合成很重要。甘氨酸甜菜碱起着重要的细胞内渗透保护剂的作用,并作为高半胱氨酸生物合成蛋氨酸的甲基供体,这是合成无处不在的甲基供体S-腺苷蛋氨酸的必需步骤。最近,由于冠心病与各种人类疾病相关,包括男性不育症,高半胱氨酸尿症,乳腺癌和代谢综合症,已经引起了广泛的医学关注。尽管重新获得了兴趣,但是由于难以获得纯化的,活性的和稳定的酶,所以该酶的生物化学表征已经落后。这篇综述文章总结了人类冠心病的医学相关性和生理作用,着重介绍了该酶的生化知识,并根据蛋白质序列与细菌胆碱氧化酶的序列比较进行了分析,从而获得了结构和生化信息。 。

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