sepiapterin

Sepiapterin is a pteridine derivative that serves as an intermediate in the biosynthesis and salvage of tetrahydrobiopterin (BH4), a crucial cofactor for the enzymes phenylalanine hydroxylase, tyrosine hydroxylase, tryptophan hydroxylase, and nitric oxide synthases. In cells, BH4 is produced through a multistep pathway beginning from GTP; sepiapterin appears in the sequence as an intermediate that can be reduced to BH4 by reductase enzymes, contributing to the maintenance of cellular BH4 pools and NOS coupling.

In the de novo BH4 pathway, dihydropterin intermediates and related pterins are transformed by enzymes such as GTP cyclohydrolase I and 6-pyruvoyl tetrahydropterin synthase, with further reduction by sepiapterin reductase and related enzymes yielding BH4. Sepiapterin can participate in BH4 salvage/recycling pathways through enzymatic reactions that ultimately replenish functional BH4 levels when needed.

Occurrence and study: Sepiapterin and related pterins are detected in various biological fluids and tissues. Their levels, alongside other pterins like biopterin and neopterin, can reflect BH4 status, oxidative stress, or abnormalities in pterin metabolism. Changes in sepiapterin concentrations have been observed in certain metabolic or enzymatic disorders affecting BH4 homeostasis, making it of interest in clinical biochemistry and metabolic research.

Chemical and practical notes: Sepiapterin is a polar, water-soluble pteridine compound. In laboratory settings, it is utilized as a substrate or tool to investigate BH4 biosynthesis, pterin metabolism, and related enzymatic activities.