Naturally-Occurring Tyrosinase Inhibitors Classified by Enzyme Kinetics and Copper Chelation
Currently, there are three major assaying methods used to validate in vitro whitening activity from natural products: methods using mushroom tyrosinase, human tyrosinase, and dopachrome tautomerase (or tyrosinase-related protein-2, TRP-2). Whitening agent development consists of two ways, melanin sy...
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MDPI AG
2023-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/9/8226 |
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| author | Hee-Do Kim Hyunju Choi Fukushi Abekura Jun-Young Park Woong-Suk Yang Seung-Hoon Yang Cheorl-Ho Kim |
| author_facet | Hee-Do Kim Hyunju Choi Fukushi Abekura Jun-Young Park Woong-Suk Yang Seung-Hoon Yang Cheorl-Ho Kim |
| author_sort | Hee-Do Kim |
| collection | DOAJ |
| description | Currently, there are three major assaying methods used to validate in vitro whitening activity from natural products: methods using mushroom tyrosinase, human tyrosinase, and dopachrome tautomerase (or tyrosinase-related protein-2, TRP-2). Whitening agent development consists of two ways, melanin synthesis inhibition in melanocytes and downregulation of melanocyte stimulation. For melanin levels, the melanocyte cell line has been used to examine melanin synthesis with the expression levels of TRP-1 and TRP-2. The proliferation of epidermal surfaced cells and melanocytes is stimulated by cellular signaling receptors, factors, or mediators including endothelin-1, α-melanocyte-stimulating hormone, nitric oxide, histamine, paired box 3, microphthalmia-associated transcription factor, pyrimidine dimer, ceramide, stem cell factors, melanocortin-1 receptor, and cAMP. In addition, the promoter region of melanin synthetic genes including tyrosinase is upregulated by melanocyte-specific transcription factors. Thus, the inhibition of growth and melanin synthesis in gene expression levels represents a whitening research method that serves as an alternative to tyrosinase inhibition. Many researchers have recently presented the bioactivity-guided fractionation, discovery, purification, and identification of whitening agents. Melanogenesis inhibition can be obtained using three different methods: tyrosinase inhibition, copper chelation, and melanin-related protein downregulation. There are currently four different types of inhibitors characterized based on their enzyme inhibition mechanisms: competitive, uncompetitive, competitive/uncompetitive mixed-type, and noncompetitive inhibitors. Reversible inhibitor types act as suicide substrates, where traditional inhibitors are classified as inactivators and reversible inhibitors based on the molecule-recognizing properties of the enzyme. In a minor role, transcription factors can also be downregulated by inhibitors. Currently, the active site copper iron-binding inhibitors such as kojic acid and chalcone exhibit tyrosinase inhibitory activity. Because the tyrosinase catalysis site structure is important for the mechanism determination of tyrosinase inhibitors, understanding the enzyme recognition and inhibitory mechanism of inhibitors is essential for the new development of tyrosinase inhibitors. The present review intends to classify current natural products identified by means of enzyme kinetics and copper chelation to exhibit tyrosinase enzyme inhibition. |
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| issn | 1661-6596 1422-0067 |
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| spelling | doaj.art-8663241737f245d3a7a9d22fefd1dc7b2023-11-17T23:07:09ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-05-01249822610.3390/ijms24098226Naturally-Occurring Tyrosinase Inhibitors Classified by Enzyme Kinetics and Copper ChelationHee-Do Kim0Hyunju Choi1Fukushi Abekura2Jun-Young Park3Woong-Suk Yang4Seung-Hoon Yang5Cheorl-Ho Kim6Molecular and Cellular Glycobiology Unit, Department of Biological Sciences, SungKyunKwan University, Seoburo 2066, Jangan-Gu, Suwon 16419, Republic of KoreaMolecular and Cellular Glycobiology Unit, Department of Biological Sciences, SungKyunKwan University, Seoburo 2066, Jangan-Gu, Suwon 16419, Republic of KoreaMolecular and Cellular Glycobiology Unit, Department of Biological Sciences, SungKyunKwan University, Seoburo 2066, Jangan-Gu, Suwon 16419, Republic of KoreaEnvironmental Diseases Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Daejeon 34141, Republic of KoreaNational Institute of Nanomaterials Technology (NINT), POSTECH, 77, Cheongam-ro, Nam-gu, Pohang-si 37676, Republic of KoreaDepartment of Medical Biotechnology, Dongguk University, Seoul 04620, Republic of KoreaMolecular and Cellular Glycobiology Unit, Department of Biological Sciences, SungKyunKwan University, Seoburo 2066, Jangan-Gu, Suwon 16419, Republic of KoreaCurrently, there are three major assaying methods used to validate in vitro whitening activity from natural products: methods using mushroom tyrosinase, human tyrosinase, and dopachrome tautomerase (or tyrosinase-related protein-2, TRP-2). Whitening agent development consists of two ways, melanin synthesis inhibition in melanocytes and downregulation of melanocyte stimulation. For melanin levels, the melanocyte cell line has been used to examine melanin synthesis with the expression levels of TRP-1 and TRP-2. The proliferation of epidermal surfaced cells and melanocytes is stimulated by cellular signaling receptors, factors, or mediators including endothelin-1, α-melanocyte-stimulating hormone, nitric oxide, histamine, paired box 3, microphthalmia-associated transcription factor, pyrimidine dimer, ceramide, stem cell factors, melanocortin-1 receptor, and cAMP. In addition, the promoter region of melanin synthetic genes including tyrosinase is upregulated by melanocyte-specific transcription factors. Thus, the inhibition of growth and melanin synthesis in gene expression levels represents a whitening research method that serves as an alternative to tyrosinase inhibition. Many researchers have recently presented the bioactivity-guided fractionation, discovery, purification, and identification of whitening agents. Melanogenesis inhibition can be obtained using three different methods: tyrosinase inhibition, copper chelation, and melanin-related protein downregulation. There are currently four different types of inhibitors characterized based on their enzyme inhibition mechanisms: competitive, uncompetitive, competitive/uncompetitive mixed-type, and noncompetitive inhibitors. Reversible inhibitor types act as suicide substrates, where traditional inhibitors are classified as inactivators and reversible inhibitors based on the molecule-recognizing properties of the enzyme. In a minor role, transcription factors can also be downregulated by inhibitors. Currently, the active site copper iron-binding inhibitors such as kojic acid and chalcone exhibit tyrosinase inhibitory activity. Because the tyrosinase catalysis site structure is important for the mechanism determination of tyrosinase inhibitors, understanding the enzyme recognition and inhibitory mechanism of inhibitors is essential for the new development of tyrosinase inhibitors. The present review intends to classify current natural products identified by means of enzyme kinetics and copper chelation to exhibit tyrosinase enzyme inhibition.https://www.mdpi.com/1422-0067/24/9/8226tyrosinase inhibitorscatalysis site structurekineticscopper chelation |
| spellingShingle | Hee-Do Kim Hyunju Choi Fukushi Abekura Jun-Young Park Woong-Suk Yang Seung-Hoon Yang Cheorl-Ho Kim Naturally-Occurring Tyrosinase Inhibitors Classified by Enzyme Kinetics and Copper Chelation International Journal of Molecular Sciences tyrosinase inhibitors catalysis site structure kinetics copper chelation |
| title | Naturally-Occurring Tyrosinase Inhibitors Classified by Enzyme Kinetics and Copper Chelation |
| title_full | Naturally-Occurring Tyrosinase Inhibitors Classified by Enzyme Kinetics and Copper Chelation |
| title_fullStr | Naturally-Occurring Tyrosinase Inhibitors Classified by Enzyme Kinetics and Copper Chelation |
| title_full_unstemmed | Naturally-Occurring Tyrosinase Inhibitors Classified by Enzyme Kinetics and Copper Chelation |
| title_short | Naturally-Occurring Tyrosinase Inhibitors Classified by Enzyme Kinetics and Copper Chelation |
| title_sort | naturally occurring tyrosinase inhibitors classified by enzyme kinetics and copper chelation |
| topic | tyrosinase inhibitors catalysis site structure kinetics copper chelation |
| url | https://www.mdpi.com/1422-0067/24/9/8226 |
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