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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Binding Sites
  • Biopterin / analogs & derivatives*
  • Biopterin / therapeutic use
  • Humans
  • Mice
  • Mice, Transgenic
  • Mitochondria / pathology
  • Mitochondrial Diseases / genetics
  • Mitochondrial Diseases / therapy*
  • Models, Biological
  • Mutation
  • Neurodegenerative Diseases / metabolism
  • Phenylketonurias / genetics
  • Phenylketonurias / therapy*
  • Reactive Oxygen Species


  • Antioxidants
  • Reactive Oxygen Species
  • Biopterin
  • sapropterin