The importance of L-phenylalanine transport and its autocrine turnover to L-tyrosine for melanogenesis in human epidermal melanocytes.
A comparative study of (14)C-labeled l-phenylalanine and (3)H-labeled L-tyrosine uptake in cultures of human melanocytes (n = 8) and keratinocytes (n = 2) identified a significantly more rapid active transport for L-phenylalanine in melanocytes, whereas the slower uptake of L-tyrosine followed a concentration-dependent gradient, confirming facilitated diffusion rather than active transport. In addition, a significantly more efficient autocrine turnover of L-phenylalanine to L-tyrosine via intracellular phenylalanine hydroxylase was demonstrated in melanocytes. The incorporation of the newly synthesized radiolabeled L-tyrosine was directly followed into the end product melanin. The presence of L-phenylalanine in the culture medium produced 40% more melanin compared to an equivalent concentration of L-tyrosine alone. The transport of extracellular L-phenylalanine and its intracellular metabolism to L-tyrosine via intracellular phenylalanine hydroxylase are coupled to calcium uptake/efflux, whereas L-tyrosine uptake is calcium independent. Taken together, our results identified for the first time the importance of autocrine calcium-dependent active l-phenylalanine uptake/turnover in melanocytes as a major pathway for melanogenesis.
Schallreuter
K U
KU
Clinical and Experimental Dermatology, Department of Biomedical Sciences, Bradford, United Kingdom. K.Schallreuter@bradford.ac.uk
Wood
J M
JM
D019898:Autocrine Communication; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology; D002478:Cells, Cultured; D000078404:Epidermal Cells; D004817:Epidermis / Q000502:physiology*; D005260:Female; D006706:Homeostasis; D006801:Humans; D008297:Male; D008543:Melanins / Q000096:biosynthesis*; D008544:Melanocytes / Q000502:physiology*; D010649:Phenylalanine / Q000378:metabolism*; D010651:Phenylalanine Hydroxylase / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism*
D008543:Melanins; D014443:Tyrosine; D010649:Phenylalanine; D010651:Phenylalanine Hydroxylase; D002118:Calcium