多巴胺β-羟化酶及其在人类健康和疾病中的遗传变异。,Journal of Neurochemistry

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多巴胺β-羟化酶及其在人类健康和疾病中的遗传变异。
Journal of Neurochemistry ( IF 4.2 ) Pub Date : 2019-10-31 , DOI: 10.1111/jnc.14893
Eugene Gonzalez-Lopez ₁ , Kent E Vrana ₁

Affiliation

多巴胺β-羟化酶（DβH）是一种重要的神经递质合成酶，可催化多巴胺形成去甲肾上腺素（NE），自1950年代被发现以来，已被广泛研究。NE在中枢神经系统和周围神经系统中均充当神经递质，并且是大脑和肾上腺髓质中肾上腺素合成的前体。去甲肾上腺素能信号传导的改变已与中枢神经系统和周围病变相关。因此，可以将循环中发现的DβH蛋白评估为多种不同疾病和疾病中去甲肾上腺素功能的标志物。在许多这些疾病中，DβH蛋白的可用性和活性被认为有助于疾病的表现或特定的症状，并且被认为处于强大的遗传控制之下。DβH蛋白由于遗传多态性的改变可能导致DβH成为限速基因，直接导致较低的NE和肾上腺素水平和疾病。随着人类基因组计划的完成和下一代测序的出现，人们对疾病中天然存在的DβH测序变异（遗传多态性）的存在有了新的认识。而且，与遗传序列结合的生物物理工具正在阐明酶中的结构-功能关系。在这篇综述中，我们讨论了遗传变异在DβH中的作用及其在健康和疾病中的作用。随着人类基因组计划的完成和下一代测序的出现，人们对疾病中天然存在的DβH测序变异（遗传多态性）的存在有了新的认识。而且，与遗传序列结合的生物物理工具正在阐明酶中的结构-功能关系。在这篇综述中，我们讨论了遗传变异在DβH中的作用及其在健康和疾病中的作用。随着人类基因组计划的完成和下一代测序的出现，人们对疾病中天然存在的DβH测序变异（遗传多态性）的存在有了新的认识。而且，与遗传序列结合的生物物理工具正在阐明酶中的结构-功能关系。在这篇综述中，我们讨论了遗传变异在DβH中的作用及其在健康和疾病中的作用。

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Dopamine beta-hydroxylase and its genetic variants in human health and disease.

Dopamine beta-hydroxylase (DβH) is an essential neurotransmitter-synthesizing enzyme that catalyzes the formation of norepinephrine (NE) from dopamine and has been extensively studied since its discovery in the 1950s. NE serves as a neurotransmitter in both the central and peripheral nervous systems and is the precursor to epinephrine synthesis in the brain and adrenal medulla. Alterations in noradrenergic signaling have been linked to both central nervous system and peripheral pathologies. DβH protein, which is found in circulation, can, therefore, be evaluated as a marker of norepinephrine function in a plethora of different disorders and diseases. In many of these diseases, DβH protein availability and activity are believed to contribute to disease presentation or select symptomology and are believed to be under strong genetic control. Alteration in the DβH protein by genetic polymorphisms may result in DβH becoming rate-limiting and directly contributing to lower NE and epinephrine levels and disease. With the completion of the human genome project and the advent of next-generation sequencing, new insights have been gained into the existence of naturally occurring DβH sequencing variants (genetic polymorphisms) in disease. Also, biophysical tools coupled with genetic sequences are illuminating structure-function relationships within the enzyme. In this review, we discuss the role of genetic variants in DβH and its role in health and disease.

更新日期：2019-11-01

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