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Disorders of Pigmentation
Published in Ayşe Serap Karadağ, Lawrence Charles Parish, Jordan V. Wang, Roxburgh's Common Skin Diseases, 2022
Michael Joseph Lavery, Charles Cathcart, Hasan Aksoy
Overview: Oculocutaneous albinism is the most common form of albinism, which is inherited in an autosomal recessive pattern. The lack of pigment is the result of deficiency in tyrosinase, which renders the individual unable to synthesize melanin despite maintaining the same number of basal melanocytes.
Comparative Anatomy, Physiology, and Biochemistry of Mammalian Skin
Published in David W. Hobson, Dermal and Ocular Toxicology, 2020
The Golgi apparatus is so well developed that many investigators believe it plays a role in melanization. The enzyme tyrosinase has been shown to be involved in melanin biosynthesis. Tyrosinase is synthesized on the ribosomes, transferred to rough endoplasmic reticulum, and then to the Golgi apparatus where it is packaged into small vesicles. In these vesicles tyrosinase begins to form an ordered pattern and melanin biosynthesis takes place, thus forming a melanosome.92–94 A spherical or ovoid cytoplasmic granule varying in size from one to several microns in diameter is called a melanin macroglobule or macromelanosome. These are frequently located in the cell body and often indent the nuclei of a melanocyte. This specific type of large melanosome has been observed in human and animal species with pigmentary disorders. There has been some disagreement about the nature and origin of these granules and studies by Nakagawa et al. have demonstrated that they are formed through autophagic processes and that their morphologic and enzymatic properties are consistent with lysosomes.95
Role of Antioxidants in Vitiligo
Published in Vineet Relhan, Vijay Kumar Garg, Sneha Ghunawat, Khushbu Mahajan, Comprehensive Textbook on Vitiligo, 2020
Mehmet Yildirim, Selma Korkmaz, İjlal Erturan
The skin is the largest organ of the body and is in constant interaction with the external environment. Melanocytes are adversely affected by the overproduction of ROS due to their specific tasks such as melanin synthesis [4,11]. Tyrosinase, a rate-limiting enzyme converting tyrosine to DOPA, that results in the formation of Dopaquinone which is intermediate product in melanin synthesis. The activity of tyrosinase decreases with increased levels of ROS. Excessive accumulation of ROS caused by chemical or physical stimuli in the epidermis of vitiligo patients results in lipid, protein, and DNA damage and increases apoptosis in melanocytes, followed by the destruction of melanocytes [11].
Functionality study of chalcone-hydroxypyridinone hybrids as tyrosinase inhibitors and influence on anti-tyrosinase activity
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2020
L. Ravithej Singh, Yu-Lin Chen, Yuan-Yuan Xie, Wei Xia, Xing-Wen Gong, Robert C. Hider, Tao Zhou
Tyrosinase is a copper-containing metalloenzyme widely distributed in animals, plants, and microorganisms and is a key and rate-limiting enzyme for melanogenesis1. It is isolated from diverse resources and its structural properties are well documented2. A di-copper centre is the common structural unit of the active site which is found in all species. Each copper ion is coordinated by three histidine residues. Further, antiferromagnetic coupling of the two copper ions renders the active site EPR inactive3. During the tyrosinase-catalysed oxidation process, the binuclear metal centre activates an O2 molecule and subsequently oxidises substrates such as l-tyrosine and l-DOPA to catecholates and benzoquinones, respectively4. As tyrosinase plays a fundamental role in the melanogenesis process, the abnormal function of this enzyme poses challenges in a range of socio-economic areas such as agriculture, food, and the pharmaceutical industry5. Tyrosinase regulates pigmentation, and abnormal expression can lead to various pigmented diseases such as freckles and age spots6. If the expression is insufficient, skin diseases such as those associated with albinism and vitiligo will occur. In fruits and vegetables, tyrosinase causes browning during post-harvest processing, transportation, and storage, affecting its quality and commercial value7.
Histidine residues at the copper-binding site in human tyrosinase are essential for its catalytic activities
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2020
Hyangsoon Noh, Sung Jun Lee, Hyun-Joo Jo, Hye Won Choi, Sungguan Hong, Kwang-Hoon Kong
Melanin biosynthesis is a complicated pathway involving chemical and enzymatic reactions and is limited to melanocytes in mammals. Tyrosinase (monophenol monooxygenase, EC 1.14.18.1) plays a pivotal role in the melanin synthesis pathway. Moreover, tyrosinase is the only human melanogenic enzyme with well-established in vivo catalytic enzyme activity1, catalysing several steps in melanin synthesis and generated by the hydroxylation of l-tyrosine2–4. Tyrosinase is a copper-containing metalloprotein belonging to the type-3 copper protein family, together with haemocyanins and catechol oxidases. These proteins are abundant in mammals, bacteria, fungi, and plants, and the active sites are highly conserved among the different species5. By synthesising melanin, tyrosinase exerts a protective function in UV-induced damage6 but can also cause hyperpigmentation, leading to aesthetic problems and melanoma. Moreover, the lack of tyrosinase activity is associated with oculocutaneous albinism (OCA) in many animal species, including humans7,8. As such, human tyrosinase is a quite attractive target for medical and industrial applications. Particularly, the screening of potent antagonists of tyrosinase and their subsequent development to drugs have attracted substantial interest in the cosmetic industry.
The 308-nm excimer laser stimulates melanogenesis via the wnt/β-Catenin signaling pathway in B16 cells
Published in Journal of Dermatological Treatment, 2019
Lili Li, Yanping Liang, Donghong Zhang, Chen Wang, Nannan Pan, Jiqiong Hong, Hewei Xiao, Zhi Xie
Melanogenesis is a complex process involving a series of enzymatically catalyzed chemical reactions and a variety of signal transduction pathways (12–14). Tyrosinase is a key enzyme in melanin synthesis and may be an important antigen for vitiligo autoimmunity (12,15). Many medications work by upregulating the expression of tyrosinase and increasing its biological activity. Our results showed that 308-nm excimer laser irradiation stimulated significant increases in melanogenesis and tyrosinase activity in B16 cells. The optimal irradiation dose was 300 mJ/cm2. This finding suggests that the laser has an optimal irradiation dose that can achieve the best re-pigmentation effect. Low-dose irradiation does not affect re-pigmentation, and high-dose irradiation might induce slight cell injury.