Department of Clinical Laboratory Medicine, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535, Japan.
TOKIWA-Bio Inc., 2-1-6 Sengen, Tsukuba 305-0047, Japan.
Int J Mol Sci. 2022 Jul 24;23(15):8153. doi: 10.3390/ijms23158153.
Sulfatases are enzymes that catalyze the removal of sulfate from biological substances, an essential process for the homeostasis of the body. They are commonly activated by the unusual amino acid formylglycine, which is formed from cysteine at the catalytic center, mediated by a formylglycine-generating enzyme as a post-translational modification. Sulfatases are expressed in various cellular compartments such as the lysosome, the endoplasmic reticulum, and the Golgi apparatus. The substrates of mammalian sulfatases are sulfolipids, glycosaminoglycans, and steroid hormones. These enzymes maintain neuronal function in both the central and the peripheral nervous system, chondrogenesis and cartilage in the connective tissue, detoxification from xenobiotics and pharmacological compounds in the liver, steroid hormone inactivation in the placenta, and the proper regulation of skin humidification. Human sulfatases comprise 17 genes, 10 of which are involved in congenital disorders, including lysosomal storage disorders, while the function of the remaining seven is still unclear. As for the genes responsible for pathogenesis, therapeutic strategies have been developed. Enzyme replacement therapy with recombinant enzyme agents and gene therapy with therapeutic transgenes delivered by viral vectors are administered to patients. In this review, the biochemical substrates, disease manifestation, and therapy for sulfatases are summarized.
硫酸酯酶是一类能够催化生物体内硫酸盐基团去除的酶，对于维持体内平衡至关重要。它们通常被一种特殊的氨基酸甲酰甘氨酸激活，这种氨基酸由甲酰甘氨酸生成酶在翻译后修饰过程中从半胱氨酸形成。硫酸酯酶在各种细胞区室中表达，如溶酶体、内质网和高尔基体。哺乳动物硫酸酯酶的底物是硫脂、糖胺聚糖和类固醇激素。这些酶在中枢和周围神经系统中维持神经元功能，在结缔组织中维持软骨形成和软骨，在肝脏中解毒外来物质和药理学化合物，在胎盘中介导类固醇激素失活，并适当调节皮肤保湿。人类硫酸酯酶由 17 个基因组成，其中 10 个与先天性疾病有关，包括溶酶体贮积症，而其余 7 个的功能仍不清楚。至于导致发病的基因，已经开发出了治疗策略。通过重组酶制剂的酶替代疗法和通过病毒载体传递的治疗性转基因的基因疗法已用于患者治疗。在这篇综述中，总结了硫酸酯酶的生化底物、疾病表现和治疗方法。
