四氢生物蝶呤的潜在治疗应用：从遗传性高苯丙氨酸血症到线粒体疾病。

Potential therapeutic applications of tetrahydrobiopterin: from inherited hyperphenylalaninemia to mitochondrial diseases.

机构信息

National Research Laboratory for Mitochondrial Signaling, Department of Physiology, Cardiovascular and Metabolic Disease Center, FIRST Mitochondrial Research Group, Inje University, Busan, Korea.

出版信息

Ann N Y Acad Sci. 2010 Jul;1201:177-82. doi: 10.1111/j.1749-6632.2010.05623.x.

DOI:10.1111/j.1749-6632.2010.05623.x

PMID:20649554

Abstract

Tetrahydrobiopterin (BH(4)) is an essential enzymatic cofactor in the formation of key neurotransmitters and nitric oxide (NO). It also has a cellular protective role as an antioxidant and scavenger of reactive nitrogen or oxygen species. Inherited hyperphenylalaninemia, which is caused by mutations in converting enzymes responsible for BH(4) synthesis, was the first reported disease implicating BH(4). Oxidative stress can also cause decreased BH(4) levels, leading to uncoupling of BH(4)-nitric oxide synthase (NOS) and diminished NO, further aggravating numerous pathologies. BH(4) deficiency is found in cardiovascular, neurodegenerative, and metabolic diseases and is also involved in aging and mitochondrial dysfunction. BH(4) supplementation successfully prevents the development or progression of these diseases and thus has valuable clinical potential.

摘要

四氢生物蝶呤（BH4）是形成关键神经递质和一氧化氮（NO）的必需酶辅因子。它还具有细胞保护作用，作为抗氧化剂和活性氮或氧物种的清除剂。由负责 BH4 合成的转化酶突变引起的遗传性高苯丙氨酸血症是第一种报道的涉及 BH4 的疾病。氧化应激也会导致 BH4 水平降低，导致 BH4-一氧化氮合酶（NOS）解偶联和 NO 减少，进一步加重许多病理。BH4 缺乏症存在于心血管、神经退行性和代谢性疾病中，也与衰老和线粒体功能障碍有关。BH4 补充成功地预防了这些疾病的发展或进展，因此具有有价值的临床潜力。