Human skin color originates from th

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) [1]. The 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 glutathione,
dopaquinone 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.

ผลลัพธ์ (อังกฤษ) 2:

Human Skin Color Originates from the Skin of the Outermost layer, the epidermis, where the
pigment-producing cells, melanocytes, are localized to Produce melanin. The Distribution Pattern of
melanin synthesized by the melanocytes Actual Determines the Color of the Skin. Melanin also plays a
role in the absorption of the CRUCIAL free Radicals Generated Within the cytoplasm and in the shielding
Host Various types of ionizing Radiation from, including UV Light. Melanin is formed by a Process
Called Melanogenesis Through a combination of enzymatically catalyzed reactions and Chemical.
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) [1]. The First Step of Melanogenesis is initiated
with tyrosine oxidation catalyzed by the Key to Dopaquinone enzyme, tyrosinase. This is the First Step
Open ACCESS
Materials two thousand and twelve, the 1,662th 5
only rate-limiting in Step 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 2-carboxylic acid-Dihydroxyindole
(DHICA), which are the Reaction Products from Dopachrome. In the Presence of cysteine ​​or glutathione,
Dopaquinone 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 and a cytoplasmic DOMAIN DOMAIN [3]. Feature observed in the tyrosinase is notable
that a Central Copper-binding DOMAIN is conserved, which contains amino acid Strictly conserved
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, melanin is synthesized, wherein the pigment.
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,. 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 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 the 2,012th Materials, 5 the 1663rd Tyrosinases catalyze the oxidations of both Monophenols (Monophenolase Activity) and o-Diphenols (Diphenolase Activity) Into reactive o-Quinones (Figure 2). Formation of melanin pigments in the, Three types of tyrosinase (Oxy-, Met-, and Deoxytyrosinase) with different Binuclear Copper Structures of the Site are active involved. Monophenolase in the 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 for further Ready 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 with Forms React 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-quinone and o-diphenol Into molecule is reduced to the Bicuprous deoxy form.