Human skin color originates from the outermost layer of the skin the epidermis where the,,,Pigment-producing, cells melanocytes are localized, to produce melanin. The distribution pattern of.Synthesized melanin by the melanocytes determines the actual color of the skin. Melanin also plays a.Crucial role in the absorption of the free radicals generated within the cytoplasm and in shielding the.Host from various types of ionizing radiation including UV, light. Melanin is formed by a process.Called melanogenesis through a combination of enzymatically catalyzed and chemical reactions.Melanogenesis takes place in, special organelles melanosomes in the, melanocytes. The biosynthetic.Pathway of melanogenesis has been elucidated where two, types of melanin are synthesized within.Melanosomes: eumelanin and pheomelanin (Figure 1) []. The 1 first step of melanogenesis is initiated.With tyrosine oxidation to dopaquinone catalyzed by the, key enzyme tyrosinase. This first step is the.OPEN ACCESS.Materials 2012 5 1662,,Only rate-limiting step in melanin synthesis because the remainder of the reaction sequence can.Proceed spontaneously at a physiological pH value [2]. After dopaquinone formation, by tyrosinase the.Compound is converted to DOPA and dopachrome through auto-oxidation. Dopa is also the substrate of.Tyrosinase and oxidized to dopaquinone again by the enzyme. Finally eumelanin is, formed through a.Series of oxidation reactions from dihydroxyindole (DHI) and dihydroxyindole-2 - carboxylic acid.(DHICA), which are the reaction products from dopachrome. In the presence of cysteine, or glutathioneDopaquinone is converted to cysteinyldopa or glutathionyldopa. Subsequently pheomelanin is, formed.Although three enzymes [tyrosinase tyrosinase-related protein, 1 and 2 (TRP1 and TRP2)] are.Involved in the melanogenesis pathway only tyrosinase, is absolutely necessary, for melanogenesis due.To its key role in the process. The enzyme is a glycoprotein located in the membrane of the.Melanosome with an inner melanosomal domain that contains the catalytic region followed by, a short.Transmembrane domain and a cytoplasmic domain [3]. The notable feature observed in tyrosinase is.That a central copper - binding domain is conserved which contains, strictly conserved amino acid.Residues including three, histidines [4]. Tyrosinase is produced only by melanocytic cells. Following.Its synthesis and subsequent processing in the endoplasmic reticulum (ER), and Golgi it is trafficked to.Melanosomes wherein the, pigment melanin is synthesized.Figure 1. Diagram of melanogenesis []. 1, TYR tyrosinase; TRP; tyrosinase related protein;DOPA 3 4-dihydroxyphenylalanine;,,,, DHICA 5 6-dihydroxyindole-2 - carboxylic, acid; DHI,, 5 6-dihydroxyindole; ICAQ indole-2 - carboxylic acid - 5 6-quinone;,,, IQ indole-5 6-quinone;,, HBTA 5-hydroxy-1 4-benzothiazinylalanine.NH2.COOH.HO.TYR.NH2.COOH.HO.HO.Tyrosine.Dopa.TYR.NH2.COOH.O.O.Dopaquinone.N.H.HO.HO.COOH.Leukodopachrome.O.O.N.H COOH.ICAQ.O NH + COOH.O.Dopachrome.TRP-2.TRP-1 N.H HO.HO.COOH.- CO2 N.H.HO.HO.DHI.TYR.O.O.N.H.DHICA.IQ.Eumelanin.Glutathione or Cysteine.NH2.COOH.HO.HO.S.H2N.COOH.N.S.NH2.HO COOH.Pheomelanin.Cysteinyldopa.HBTA.Mixed-melanin.Eumelanogenesis Pheomelanogenesis.NH2.COOH.HO.TYR.NH2.COOH.HO.HO.Tyrosine.Dopa.TYR.NH2.COOH.O.O.Dopaquinone.N.H.HO.HO.COOH.Leukodopachrome.O.O.N.H COOH.ICAQ.O NH + COOH.O.Dopachrome.TRP-2.TRP-1 N.H HO.HO.COOH.- CO2 N.H.HO.HO.DHI.TYR.O.O.N.H.DHICA.IQ.Eumelanin.Glutathione or Cysteine.NH2.COOH.HO.HO.S.H2N.COOH.N.S.NH2.HO COOH.Pheomelanin.Cysteinyldopa.HBTA.Mixed-melanin.Eumelanogenesis Pheomelanogenesis.Materials 2012 5 1663,,Tyrosinases catalyze the oxidations of both monophenols (monophenolase activity) and o-diphenols.(diphenolase activity) into reactive o-quinones (Figure 2). In the formation of, melanin pigments three.Types of tyrosinase (oxy -, met -, and deoxytyrosinase) with different binuclear copper structures of the.Active site are involved. In the monophenolase cycle the monophenol, can react only with the oxy form.And be catalyzed to a coordinated o-diphenol which is, oxidized to the o-quinone resulting in, a deoxy.Form ready for further dioxygen binding. Oxytyrosinase, is then regenerated after, the binding of.Molecular oxygen to deoxytyrosinase. If only o-diphenol is present (the diphenolase cycle), both the.Oxy and met forms react, with o-diphenol oxidizing it to the o-quinone. O-diphenol binds to the oxy.Form and is oxidized to o-quinone yielding the, met form of the enzyme. The latter form transforms.Another o-diphenol molecule into o-quinone and is reduced to the bicuprous deoxy form.
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