Shanghai Frontiers Science Center for Chinese Medicine Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Institute of Science, Technology and Humanities, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Biosensors (Basel). 2021 Aug 23;11(8):290. doi: 10.3390/bios11080290.
Tyrosinase (TYR, E.C. 1.14.18.1), a critical enzyme participating in melanogenesis, catalyzes the first two steps in melanin biosynthesis including the -hydroxylation of L-tyrosine and the oxidation of L-DOPA. Previous pharmacological investigations have revealed that an abnormal level of TYR is tightly associated with various dermatoses, including albinism, age spots, and malignant melanoma. TYR inhibitors can partially block the formation of pigment, which are always used for improving skin tone and treating dermatoses. The practical and reliable assays for monitoring TYR activity levels are very useful for both disease diagnosis and drug discovery. This review comprehensively summarizes structural and enzymatic characteristics, catalytic mechanism and substrate preference of TYR, as well as the recent advances in biochemical assays for sensing TYR activity and their biomedical applications. The design strategies of various TYR substrates, alongside with several lists of all reported biochemical assays for sensing TYR including analytical conditions and kinetic parameters, are presented for the first time. Additionally, the biomedical applications and future perspectives of these optical assays are also highlighted. The information and knowledge presented in this review offer a group of practical and reliable assays and imaging tools for sensing TYR activities in complex biological systems, which strongly facilitates high-throughput screening TYR inhibitors and further investigations on the relevance of TYR to human diseases.
酪氨酸酶（TYR，EC 1.14.18.1）是一种参与黑色素生成的关键酶，催化黑色素生物合成的前两个步骤，包括 L-酪氨酸的 -羟化和 L-DOPA 的氧化。先前的药理学研究表明，TYR 水平异常与各种皮肤病密切相关，包括白化病、老年斑和恶性黑色素瘤。TYR 抑制剂可以部分阻断色素的形成，常用于改善肤色和治疗皮肤病。监测 TYR 活性水平的实用可靠的测定方法对于疾病诊断和药物发现都非常有用。本综述全面总结了 TYR 的结构和酶学特性、催化机制和底物偏好，以及用于检测 TYR 活性的生化测定方法的最新进展及其在生物医学中的应用。首次提出了各种 TYR 底物的设计策略，以及用于检测 TYR 的所有生化测定方法的列表，包括分析条件和动力学参数。此外，还强调了这些光学测定方法的生物医学应用和未来前景。本综述中提供的信息和知识为在复杂生物系统中检测 TYR 活性提供了一组实用可靠的测定方法和成像工具，有力地促进了 TYR 抑制剂的高通量筛选以及对 TYR 与人类疾病相关性的进一步研究。
