Melanogenesis

A potent inhibitor of melanogenesis is hydroquinone. A naturally occurring derivative of hydroquinone is arbutin.

For the synthesis of melanin 3 key enzymes are important:

Tyrosinase is the key enzyme in melanogenesis. It catalyses two different reactions. First, it converts tyrosine into dopa and then dopa into DOP-quinone. The melanin synthesis rate is largely controlled by systems that regulate the production and activity of tyrosinase. The synthesis process takes place in the rough endoplasmic reticulum and in the Golgi apparatus of melanocytes. DOPAquinone is oxidized and polymerized to phaeomelanin.

DOPAchrome automerase (DCT) is an enzyme that converts DOPAchrome into DHI-2-carboxylic acid (DHI-carboxylic-acid = DHICA), which forms another type of melanin, the light brown DIICA-melanin.

Tyrosinase-related protein-1 (TYRP1) is an enzyme crucial for the transport of tyrosine to the melanosomes

After synthesis, melanin is stored in intracellular granules called melanosomes. The size of these granules varies depending on the pigmentation type. The darker the skin is pigmented, the larger they are.

The maturation of melanosomes takes place in the melanocytes in 4 stages. For the transformation of stage I melanosomes into stage II melanosomes, the structural protein MART1 is absolutely necessary.

Melanin is formed in the skin in increased quantities under the influence of sunlight (see chromophores below) and serves as light protection against the damaging influence of UV radiation. Furthermore, the proliferation and differentiation of melanocytes and thus of melanin is increased by growth factors which are formed by keratinocytes and fibroblasts of the skin. Antagonistically, the thick head 1 protein (DKK-1) acts via the WNT/beta-catein signaling pathway (see below catenins), which is produced in large quantities in the fibroblasts of the palms.

The pigment phenotype itself is subject to a complex genetic programme. Essentially, pigmentation is controlled by the melanocortin 1 receptor (MC1R) gene, which in turn encodes MC1R, a receptor coupled to a G protein (guanine nucleotide-binding proteins) on the surface of melanocytes. MC1-R is regulated by the stimulating pituitary hormones melanocyte-stimulating hormone (MSH), beta-lipotropin and ACTH on the one hand and antagonistically by the agouti-signalling protein on the other.

The synthesis of melanin can be disturbed by genetic predisposition or by genetic damage acquired over time. If production is blocked, the dyes in the skin and eyes are also missing, which can lead to different types of pigment defects (see depigmentation below). An analogously induced overproduction of melanin leads to the pathological condition of hyperpigmentation.

1. Bin BH et al (2016) The Development of Sugar-Based anti-Melanogenic Agents. Int J Mol Sci 17:583.
2. D'Mello SA e al.(2016) Signaling Pathways in Melanogenesis. Int J Mol Sci 17. pii: E1144.
3. Gunia-Krzyżak A et al. (2016) Melanogenesis Inhibitors: Strategies for Searching for and Evaluation of Active Compounds. Curr Med Chem PubMed PMID: 27356545.