Tetrahydrobioterin (BH4) Pathway: From Metabolism to Neuropsychiatry.
Tetrahydrobioterin (BH4) Pathway: From Metabolism to Neuropsychiatry.
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DOI：
10.2174/1570159x18666200729103529
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发表时间：
2021
影响因子：
5.3
通讯作者：
Vancassel S
中科院分区：
文献类型：
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作者：
Fanet H;Capuron L;Castanon N;Calon F;Vancassel S
四氢双蝶呤 (BH4) 是合成血清素、多巴胺和一氧化氮所需的关键酶辅因子。 BH4 对于外周和中枢水平的许多生理过程至关重要，例如血管形成、炎症、葡萄糖稳态、氧化应激调节和神经传递。 BH4 从头合成涉及三种酶的连续激活，主要控制点是 GTP 环水解酶 I (GCH1)。互补的回收和再循环途径可确保 BH4 水平严格保持在体内的生理范围内。尽管BH4的转运方式及其在外周给药后进入大脑的能力仍然存在争议，但数据显示BH4治疗后大脑中的水平有所增加。现有证据表明 GCH1 表达和 BH4 合成受到免疫因素（尤其是促炎细胞因子）的刺激。 BH4 一旦产生，可以充当抗炎分子和自由基清除剂，防止氧化应激。同时，BH4 容易发生自氧化，导致超氧自由基的释放，导致炎症过程，并产生 BH2（BH4 的非活性形式），从而降低其生物利用度。 BH4 水平的变化已在许多病理情况下得到记录，包括阿尔茨海默病、帕金森病和抑郁症，其中描述了氧化应激增加、炎症和单胺能功能的改变。本综述旨在提供从临床前到临床研究的代谢和 BH4 在脑功能中的作用的最新知识，并解决一些治疗意义。
Tetrahydrobipterin (BH4) is a pivotal enzymatic cofactor required for the synthesis of serotonin, dopamine and nitric oxide. BH4 is essential for numerous physiological processes at periphery and central levels, such as vascularization, inflammation, glucose homeostasis, regulation of oxidative stress and neurotransmission. BH4 de novo synthesis involves the sequential activation of three enzymes, the major controlling point being GTP cyclohydrolase I (GCH1). Complementary salvage and recycling pathways ensure that BH4 levels are tightly kept within a physiological range in the body. Even if the way of transport of BH4 and its ability to enter the brain after peripheral administration is still controversial, data showed increased levels in the brain after BH4 treatment. Available evidence shows that GCH1 expression and BH4 synthesis are stimulated by immunological factors, notably pro-inflammatory cytokines. Once produced, BH4 can act as an anti-inflammatory molecule and scavenger of free radicals protecting against oxidative stress. At the same time, BH4 is prone to autoxidation, leading to the release of superoxide radicals contributing to inflammatory processes, and to the production of BH2, an inactive form of BH4, reducing its bioavailability. Alterations in BH4 levels have been documented in many pathological situations, including Alzheimer's disease, Parkinson's disease and depression, in which increased oxidative stress, inflammation and alterations in monoaminergic function are described. This review aims at providing an update of the knowledge about metabolism and the role of BH4 in brain function, from preclinical to clinical studies, addressing some therapeutic implications.
DOI：
10.4196/kjpp.2014.18.2.129
发表时间：
2014-04
期刊：
The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology
影响因子：
--
作者：
Aryal B;Lee JK;Kim HR;Kim HG
通讯作者：
Kim HG