L-tyrosine and L-dihydroxyphenylalanine as hormone-like regulators of melanocyte functions

Abstract

There is evidence that L-tyrosine and L-dihydroxyphenylalanine (L-DOPA), besides serving as substrates and intermediates of melanogenesis, are also bioregulatory agents acting not only as inducers and positive regulators of melanogenesis but also as regulators of other cellular functions. These can be mediated through action on specific receptors or through non-receptor-mediated mechanisms. The substrate induced (L-tyrosine and/or L-DOPA) melanogenic pathway would autoregulate itself as well as regulate the melanocyte functions through the activity of its structural or regulatory proteins and through intermediates of melanogenesis and melanin itself. Dissection of regulatory and autoregulatory elements of this process may elucidate how substrate-induced autoregulatory pathways have evolved from prokaryotic or simple eukaryotic organisms to complex systems in vertebrates. This could substantiate an older theory proposing that receptors for amino acid-derived hormones arose from the receptors for those amino acids, and that nuclear receptors evolved from primitive intracellular receptors binding nutritional factors or metabolic intermediates.

Figure 1. Scheme showing metabolic transformation of L-tyrosine and its precursor L-phenylalanine to several bioregulatory molecules

In addition of being transformed to catecholamines and melanins, L-tyrosine and L-DOPA can potentially be estrified as shown in the lower box, where R1 and R2 = phosphate, sulphate, glucuronide, acetyl or nitrate.

Figure 2. Scheme show enzymatic steps of sequential transformation of L-tyrosine and L-DOPA to melanin pigments

Figure 3. Potential modifications of L-tyrosine and L-DOPA and it oxidation products with predicted physiological significance

Figure 4. Proposed mechanism of L-tyrosine and L-DOPA regulation of the melanocyte phenotype

GPCR: membrane bound receptors including G-protein coupled receptor; NR: nuclear receptors; Tyr: tyrosinase; TRP: tyrosinase related proteins; PH: phenylalanine hydroxylase, TH: tyrosine hydroxylase,. Solid lines shows well established or most probable pathways, dashed line shows hypothetic interactions.