(6R)-tetrahydrobiopterin increases the activity of tryptophan hydroxylase in rat raphe slices

J Neurochem. 1986 Nov;47(5):1544-7. doi: 10.1111/j.1471-4159.1986.tb00792.x.


The effects of (6R)- and (6S)-tetrahydrobiopterin (BPH4), tetrahydroneopterin, and 6-methyltetrahydropterin on the activity of tryptophan hydroxylase were investigated in rat raphe slices. The activity of tryptophan hydroxylase was estimated by measurement of 5-hydroxytryptophan (5-HTP) formation under inhibition of aromatic L-amino acid decarboxylase with use of HPLC-fluorometric detection. (6R)-BPH4 (the naturally occurring form) at 42 microM, tetrahydroneopterin at 50 microM, and 6-methyltetrahydropterin at 100 microM increased tryptophan hydroxylase activity to 350, 145, and 146% of control values, respectively. (6S)-BPH4, however, had no significant effects on tryptophan hydroxylase activity. These results suggest that tryptophan hydroxylase is subsaturating in vivo for the naturally occurring cofactor, (6R)-BPH4, and that the concentration of (6R)-BPH4 may play an important role for the regulation of tryptophan hydroxylase activity in vivo.

MeSH terms

  • 5-Hydroxytryptophan / metabolism
  • Animals
  • Biopterin / analogs & derivatives*
  • Biopterin / pharmacology
  • Male
  • Pterins / pharmacology
  • Raphe Nuclei / drug effects
  • Raphe Nuclei / enzymology*
  • Rats
  • Rats, Inbred Strains
  • Tryptophan Hydroxylase / metabolism*


  • Pterins
  • Biopterin
  • 5-Hydroxytryptophan
  • 6-methyltetrahydropterin
  • Tryptophan Hydroxylase
  • sapropterin