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Potential therapeutic applications of tetrahydrobiopterin: from inherited hyperphenylalaninemia to mitochondrial diseases
Author(s) -
Kim Hyoung K.,
Ha Seung H.,
Han Jin
Publication year - 2010
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2010.05623.x
Subject(s) - tetrahydrobiopterin , hyperphenylalaninemia , reactive nitrogen species , oxidative stress , biopterin , nitric oxide , nitric oxide synthase , reactive oxygen species , oxidative phosphorylation , chemistry , mitochondrion , biochemistry , mitochondrial disease , enzyme , pharmacology , medicine , phenylalanine , mitochondrial dna , amino acid , gene
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.