Inhibition by analogues of L-tyrosine transport by B16/F10 melanoma cells.
The effect of a number of L-tyrosine (L-Tyr) analogues on L-Tyr uptake by B16/F10 malignant melanocytes is reported. This amino acid can be taken up by two of the most ubiquitous transport systems found in animals cells, L and presumably ASC. L-Tyr analogues devoid of the amino group, like p-hydroxyphenyl pyruvic acid and related compounds, and L-Tyr analogues devoid of the carboxyl group, such as tyramine, do not affect L-Tyr uptake. The other aromatic amino acids, L-Phe and L-Trp, and the L-Tyr analogues DL-m-Tyr, L-diiodotyrosine and L-dopa, strongly inhibit the uptake of L-Tyr. This suggests that these chemicals are transported more efficiently than L-Tyr. The ASC system does not show stereospecificity, but the L system has greater affinity for L-Tyr than for D-Tyr. The ASC system also has greater affinity for tyrosine isomers with the hydroxyl group in the ortho and meta positions. The presence of a methyl group at the alpha-carbon of L-Tyr and L-dopa also increases the affinity of the ASC system for these agents. In contrast, alpha-methylation decreases the affinity of the L system in comparison to L-Tyr. Finally, L-Tyr esters do not inhibit, but stimulate the transport of L-Tyr, mainly by the ASC system.
Jara
J R
JR
Department of Biochemistry and Molecular Biology, Facultad de Medicina, Universidad de Murcia, Spain.
Martinez-Liarte
J H
JH
Solano
F
F
D026905:Amino Acid Transport Systems; D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism*; D004295:Dihydroxyphenylalanine / Q000494:pharmacology; D004952:Esters / Q000494:pharmacology; D008544:Melanocytes / Q000187:drug effects* / Q000378:metabolism; D008546:Melanoma, Experimental / Q000378:metabolism / Q000473:pathology*; D008781:Methyltyrosines / Q000494:pharmacology; D051379:Mice; D009363:Neoplasm Proteins / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism; D019805:alpha-Methyltyrosine
D026905:Amino Acid Transport Systems; D000596:Amino Acids; D002352:Carrier Proteins; D004952:Esters; D008781:Methyltyrosines; D009363:Neoplasm Proteins; D014443:Tyrosine; D004295:Dihydroxyphenylalanine; D019805:alpha-Methyltyrosine