O-methylation of L-dopa in melanin metabolism and the presence of catechol-O-methyltransferase in melanocytes.
O-Methylation of L-dopa was investigated as a possible regulatory mechanism in melanin metabolism. The methylation product of L-dopa, 3-O-methoxytyrosine was detected in extracts of cultured human melanocytes. The enzyme catechol-O-methyltransferase is responsible for this O-methylation and that of the dihydroxyindolic intermediates of melanogenesis. The enzyme is present in melanocytes in its soluble and membrane-bound isoforms. Immuno-electron microscopy suggests the presence of the membrane-bound enzyme in the endoplasmic reticulum. This localization may indicate a role of catechol-O-methyltransferase in protecting the melanocyte against reactive dihydroxyphenolic intermediates of melanogenesis leaking from the melanogenic compartments. On the other hand, the O-methylation of L-dopa may serve as a regulatory point in melanogenesis during early stage of tyrosinase processing in the endoplasmic reticulum.
Smit
N
N
Department of Dermatology, Academic Medical Center, Amsterdam, The Netherlands.
Tilgmann
C
C
Karhunen
T
T
Slingerland
R
R
Ulmanen
I
I
Westerhof
W
W
Pavel
S
S
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D002394:Catechol O-Methyltransferase / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D007980:Levodopa / Q000378:metabolism*; D008543:Melanins / Q000378:metabolism*; D008544:Melanocytes / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism / Q000648:ultrastructure; D008545:Melanoma / Q000473:pathology; D008565:Membrane Proteins / Q000378:metabolism; D008745:Methylation; D016253:Microscopy, Immunoelectron; D014442:Monophenol Monooxygenase / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D013347:Subcellular Fractions / Q000201:enzymology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D007527:Isoenzymes; D008543:Melanins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D007980:Levodopa; D014442:Monophenol Monooxygenase; D002394:Catechol O-Methyltransferase; D013755:Tetradecanoylphorbol Acetate; D015056:1-Methyl-3-isobutylxanthine