Tetrahydrobiopterin Biosynthesis as an Off-Target of Sulfa Drugs

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.