Melanin, synthesis

N-ras, H-ras, K-ras Signal transduction pathway Inhibition of cell proliferation and colony formation change in morphology, enhanced melanin synthesis decrease of in vivo tumorigenicity... 

V. Melanin Synthesis—The Role of Tyrosinase and Related Proteins.158... 

V. MELANIN SYNTHESIS—THE ROLE OF TYROSINASE AND RELATED PROTEINS... 

The pathway of melanin synthesis starts from the amino acid tyrosine (Fig. 1). The first two reactions are catalyzed by the copper-containing enzyme tyrosinase (EC 1.14.18.1). Tyrosine is hydroxylated to 3,4-dihy-... 

Polyphenol oxidase occurs within certain mammalian tissues as well as both lower (46,47) and higher (48-55) plants. In mammalian systems, the enzyme as tyrosinase (56) plays a significant role in melanin synthesis. The PPO complex of higher plants consists of a cresolase, a cate-cholase and a laccase. These copper metalloproteins catalyze the one and two electron oxidations of phenols to quinones at the expense of 02. Polyphenol oxidase also occurs in certain fungi where it is involved in the metabolism of certain tree-synthesized phenolic compounds that have been implicated in disease resistance, wound healing, and anti-nutrative modification of plant proteins to discourage herbivory (53,55). This protocol presents the Triton X-114-mediated solubilization of Vida faba chloroplast polyphenol oxidase as performed by Hutcheson and Buchanan (57). 

The nutritional and medical importance of ascorbate is well known. Besides this, it is also used as, e.g., a skin-whitening agent in cosmetics in Japan due to its in vivo inhibitory effect on melanin synthesis.129... 

A nonubiquitous organelle, the melanosome, is specialized for melanin synthesis. It is somewhat similar to the lysosome, and the resident proteins are derived from the endocytic pathway. A sorting signal, the NQPLLT, was found in the cytoplasmic protein of a human membrane protein (Vijayasaradhi et al., 1995). 

Tyrosinase Melanin synthesis Fungi, mammals Robb (1984)... 

The presence of catechols and more complex, oxidizable polyphenols in nature is widespread, and their functions are not limited to chemical defense. However, biological control of their oxidation is usually a feature of their function, as it is (1) in melanin synthesis,3 (2) in immunologically mediated delayed-type hypersensitivity responses,4 (3) in the hardening or curing of arthropod secretions (for example, as in the surface attachment adhesives of the barnacle and in tanning of the cuticle in insects),5 as well as (4) in defensive mechanisms in higher plants, particularly in the unleashing of immediate necrotrophic responses.6... 

Albinism <3 Melanin synthesis from tyrosine Tyrosine 3-monooxygenase (tyrosinase) Lack of pigmentation white hair, pink skin... 

Lee CH, Chung MC, Lee HJ, Bae KS, Kho YH (1997) MR566A and MR566B, New Melanin Synthesis Inhibitors Produced by Trichoderma harzianum I. Taxonomy, Fermentation, Isolation and Biological Activities. J Antibiot 50 469... 

The following example describes the results of the dereplication of an HTP fraction library for inhibition of melanin formation in an in vitro assay with a B16 cell line [54]. Briefly, following the inhibition and cell viability assay, the active organic extract from the whole plant of Mallotus repandus was fractionated with HTP. All of the HTP fractions were tested for melanin inhibitory activities. As shown in Figure 8, there are three major peaks exhibiting > 50% inhibitions of melanin synthesis and seven minor peaks exhibiting weaker inhibitions. The sharp activity peaks indicate the quality of the separations, which distributed the active components in three to five cells. 

Further analysis of the UV spectrum revealed that this compound is a gallic acid derivative. A search of the Dictionary of Natural Products for molecular ion and plant genus name leads to the identification of a known compound - Pterocaryanin B. The compounds with poly-hydroxyl groups in their structures are very well known as tyrosinase inhibitors and are responsible for the inhibition of melanin synthesis. Therefore, no further isolation was necessary. 

Ty initiates melanin synthesis by the hydroxylation of L-tyrosine to 3,4-dihydroxyphenylalanine (Dopa) and the oxidation of dopa to dopaquinone. In the presence of L-cysteine, dopaquinone rapidly combines with the thiol group to form cysteinyldopas, which undergo nonen-zymatic conversion and polymerization to pheomelanin via benzothiazine intermediates. In the absence of thiol groups, dopaquinone very rapidly undergoes conversion to dopachrome, which is transformed to 5,6-dihydroxyindole-2-carboxylic acid (DHICA) by dopachrome tautomerase. Alternatively, dopachrome is converted nonenzymatically to 5,6-dihydroxyindole (DHI). Oxidation of DHICA and DHI to the corresponding quinones and subsequent polymerization leads to eumelanins. It is still questionable if Ty is involved in this step. 

MSHs consist of three peptide hormones a-MSH, 3-MSH, and y-MSH, which are secreted by intermediate lobe of the pituitary gland. They are cleaved from the same precursor peptide as ACTH. Their basic function is stimulation of melanocytes to darken skin and stimulation of melanin synthesis to darken the skin and hair. They also have been found to be released in the brain affecting appetite, sexual arousal, and many other functions. 

The authors suggested that the effect was due to impaired melanin synthesis. 

The authors speculated that the increased concentrations of dopamine may have interfered with melanin synthesis. 

Melanin synthesis of the arthropods is essential for defense and development. The melaniza-tion cascade is activated by bacterial PG or fungal /3-1,3-glucan. Lee and co-workers reported that the tetrasaccharide tetrapeptide functioned as a competitive inhibitor of the natural PG-induced melanization reaction [151]. By using a tetrasaccharide tetrapeptide-coupled column, the Tenebrio molitor PG recognition protein (Tm-PGRP) was purified without activation of the prophenoloxidase. 

Ascorbate, because of its in vivo inhibitory action on melanin synthesis is also used as a skinwhitening agent in cosmetics (e. g., in Japan) [171]. Glycoside 93 was tested in vitro and in... 

Fig. 36 Inhibitory effects of trifolirhizin (2), kurarinol (3), and kuraridinol (9) from Sophora flavescens on tyrosinase and melanin synthesis...

Drug-induced pigmentation on the skin, hair, nails, and mucous membranes is a result of melanin synthesis, increased lipofuscin synthesis, or post-inflammatory pigmentation. 

Melanin Synthesis. Tyrosinase is a copper-containing enzyme that is present in melanocytes and catalyzes the synthesis of melanin. Starting with L-dopa as a substrate, tyrosi-... 

More often than not, it takes 3-4 months of daily applications of AHA creams alone to get a clinical result. AHAs are not renowned for their anti-tyrosinase action they limit melanin synthesis mainly through their antioxidant power and increase the turnover and renewal of cells laden with pigment. Using just AHA creams as the only form of treatment for melasma is disappointing. 

There is no point combining hydroquinone and AHAs in a peel solution, as hydroquinone has a tyrosinase-inhibiting action that can only establish itself gradually and act on the first biochemical stages of melanin synthesis. 

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