Maintenance of cellular tetrahydrobiopterin homeostasis

Tetrahydrobiopterin (BH4) is a multifunctional cofactor of aromatic amino acid hydroxylases and nitric oxide synthase (NOS) as well as an intracellular antioxidant in animals. Through regulation of NOS activity BH4 plays a pivotal role not only in a variety of normal cellular functions but also in t...

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Bibliographic Details
Published in:BMB reports 2010, 43(9), , pp.584-592
Main Authors: Kim, H.L., Inje University, Gimhae, Republic of Korea, Park, Y.S., Inje University, Gimhae, Republic of Korea
Format: Article
Language:English
Subjects:
BIOSINTESIS
BIOSYNTHESE
BIOSYNTHESIS
Endothelial dysfunction
Neurodegenerative diseases
Nitric oxide synthase
REGENERACION
REGENERATION
Tetrahydrobiopterin
화학
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Summary:Tetrahydrobiopterin (BH4) is a multifunctional cofactor of aromatic amino acid hydroxylases and nitric oxide synthase (NOS) as well as an intracellular antioxidant in animals. Through regulation of NOS activity BH4 plays a pivotal role not only in a variety of normal cellular functions but also in the pathogenesis of cardiovascular and neurodegenerative diseases, which develop under oxidative stress conditions. It appears that a balanced interplay between BH4 and NOS is crucial for cellular fate. If cellular BH4 homeostasis maintained by BH4 synthesis and regeneration fails to cope with increased oxidative stress, NOS is uncoupled to generate superoxide rather than NO and, in turn, exacerbates impaired BH4 homeostasis, thereby leading to cell death. The fundamental biochemical events involved in the BH4-NOS interplay are essentially the same, as revealed in mammalian endothelial, cardiac, and neuronal cells. This review summarizes information on the cellular BH4 homeostasis in mammals, focusing on its regulation under normal and oxidative stress conditions.
ISSN:1976-6696
1976-670X
DOI:10.5483/BMBRep.2010.43.9.584