The importance of L-phenylalanine transport and its autocrine turnover to L-tyrosine for melanogenesis in human epidermal melanocytes

A comparative study of C-14-labeled L-phenylalanine and H-3-labeled L-tyros ine uptake in cultures of human melanocytes (n = 8) and keratinocytes (n = 2) identified a significantly more rapid active transport for L-phenylalani ne in melanocytes, whereas the slower uptake of L-tyrosine followed a conce ntration-dependent gradient, confirming facilitated diffusion rather than a ctive transport. In addition, a significantly more efficient autocrine turn over of L-phenylalanine to L-tyrosine via intracellular phenylalanine hydro xylase was demonstrated in melanocytes. The incorporation of the newly synt hesized 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 metabo lism 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 o f autocrine calcium-dependent active L-phenylalanine uptake/turnover in mel anocytes as a major pathway for melanogenesis. (C) 1999 Academic Press.