Tetrahydrobiopterin: beyond its traditional role as a cofactor

Tuany Eichwald, Lucila de Bortoli da Silva, Ananda Christina Staats Pires, Laís Niero, Erick Schnorrenberger, Clovis Colpani Filho, Gisele Espíndola, Wei Lin Huang, Gilles J. Guillemin, José E. Abdenur, Alexandra Latini*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

10 Citations (Scopus)
1 Downloads (Pure)

Abstract

Tetrahydrobiopterin (BH4) is an endogenous cofactor for some enzymatic conversions of essential biomolecules, including nitric oxide, and monoamine neurotransmitters, and for the metabolism of phenylalanine and lipid esters. Over the last decade, BH4 metabolism has emerged as a promising metabolic target for negatively modulating toxic pathways that may result in cell death. Strong preclinical evidence has shown that BH4 metabolism has multiple biological roles beyond its traditional cofactor activity. We have shown that BH4 supports essential pathways, e.g., to generate energy, to enhance the antioxidant resistance of cells against stressful conditions, and to protect from sustained inflammation, among others. Therefore, BH4 should not be understood solely as an enzyme cofactor, but should instead be depicted as a cytoprotective pathway that is finely regulated by the interaction of three different metabolic pathways, thus assuring specific intracellular concentrations. Here, we bring state-of-the-art information about the dependency of mitochondrial activity upon the availability of BH4, as well as the cytoprotective pathways that are enhanced after BH4 exposure. We also bring evidence about the potential use of BH4 as a new pharmacological option for diseases in which mitochondrial disfunction has been implicated, including chronic metabolic disorders, neurodegenerative diseases, and primary mitochondriopathies.

Original languageEnglish
Article number1037
Pages (from-to)1-27
Number of pages27
JournalAntioxidants
Volume12
Issue number5
DOIs
Publication statusPublished - 3 May 2023

Bibliographical note

Copyright the Author(s) 2023. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

  • antioxidant
  • inflammation
  • memory
  • mitochondrial enhancer
  • neopterin
  • oxidative stress
  • sepiapterin

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