Cytotoxicity of 6-biopterin to human melanocytes.
(6R)5,6,7,8 tetrahydrobiopterin (6-BH4) is an important cofactor in the regulation of melanogenesis in melanocytes, where it controls: (a) the supply of L-tyrosine from L-phenylalanine via phenylalanine hydroxylase, and (b) regulates directly dopaquinone formation from L-tyrosine via tyrosinase. 6-BH4 undergoes redox-cycling by its oxidation to quinonoid dihydrobiopterin (qBH2) and to 6-biopterin through consecutive two electron oxidation reactions. The oxidized cofactor 6-biopterin (0.2 x 10(-6) M) is extremely cytotoxic to human melanocytes under in vitro conditions. Consequently, its reduction to 6-BH4 via q-BH2 is essential to melanocyte viability. In addition, the results herein show for the first time that human thioredoxin reductase has the capacity to reduce 6-biopterin to q-BH2 where further reduction to 6-BH4 follows via dihydropteridine reductase or reduced glutathione.
Schallreuter
K U
KU
Department of Dermatology, University of Hamburg, Germany.
Büttner
G
G
Pittelkow
M R
MR
Wood
J M
JM
Swanson
N N
NN
Körner
C
C
D001708:Biopterins / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008544:Melanocytes / Q000166:cytology* / Q000187:drug effects; D012867:Skin / Q000166:cytology / Q000187:drug effects
D001708:Biopterins