Tetrahydrobiopterin Biosynthesis as an Off-Target of Sulfa Drugs

Author:

Haruki Hirohito1,Pedersen Miriam Grønlund1,Gorska Katarzyna Irena1,Pojer Florence2,Johnsson Kai1

Affiliation:

1. EPFL, Institute of Chemical Sciences and Engineering, Institute of Bioengineering, National Centre of Competence in Research (NCCR) in Chemical Biology, 1015 Lausanne, Switzerland.

2. École Polytechnique Fédérale de Lausanne (EPFL), Global Health Institute, 1015 Lausanne, Switzerland.

Abstract

Going Off-Target Sulfamethoxazole is a widely used sulfa-drug often used at high doses in the treatment of Pneumocytis pneumonia (PCP) in immunocompromised individuals. Haruki et al. (p. 987 ) show that sulfamethoxazole and certain other sulfa drugs inhibit the enzyme septiapterin reductase that catalyzes the final step in the biosynthesis of tetrahydrobiopterin (BH4). BH4 is a cofactor in the biosynthesis of neurotransmitters such as serotonin and dopamine. In cell culture, sulfamethoxazole lowered neurotransmitter levels through depletion of BH4, which may explain central nervous system side effects associated with PCP treatment.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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