Mammalian Sulfatases: Biochemistry, Disease Manifestation, and Therapy
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-genera...
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MDPI AG
2022-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/15/8153 |
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| author | Ryuichi Mashima Mahito Nakanishi |
| author_facet | Ryuichi Mashima Mahito Nakanishi |
| author_sort | Ryuichi Mashima |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T05:23:09Z |
| format | Article |
| id | doaj.art-51364f70bce64b7b9dac4dee3d4ce123 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T05:23:09Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-51364f70bce64b7b9dac4dee3d4ce1232023-12-03T12:38:40ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-07-012315815310.3390/ijms23158153Mammalian Sulfatases: Biochemistry, Disease Manifestation, and TherapyRyuichi Mashima0Mahito Nakanishi1Department of Clinical Laboratory Medicine, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535, JapanTOKIWA-Bio Inc., 2-1-6 Sengen, Tsukuba 305-0047, JapanSulfatases 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.https://www.mdpi.com/1422-0067/23/15/8153sulfatasepost-translational modificationformylglycinebiochemistrygene therapy |
| spellingShingle | Ryuichi Mashima Mahito Nakanishi Mammalian Sulfatases: Biochemistry, Disease Manifestation, and Therapy International Journal of Molecular Sciences sulfatase post-translational modification formylglycine biochemistry gene therapy |
| title | Mammalian Sulfatases: Biochemistry, Disease Manifestation, and Therapy |
| title_full | Mammalian Sulfatases: Biochemistry, Disease Manifestation, and Therapy |
| title_fullStr | Mammalian Sulfatases: Biochemistry, Disease Manifestation, and Therapy |
| title_full_unstemmed | Mammalian Sulfatases: Biochemistry, Disease Manifestation, and Therapy |
| title_short | Mammalian Sulfatases: Biochemistry, Disease Manifestation, and Therapy |
| title_sort | mammalian sulfatases biochemistry disease manifestation and therapy |
| topic | sulfatase post-translational modification formylglycine biochemistry gene therapy |
| url | https://www.mdpi.com/1422-0067/23/15/8153 |
| work_keys_str_mv | AT ryuichimashima mammaliansulfatasesbiochemistrydiseasemanifestationandtherapy AT mahitonakanishi mammaliansulfatasesbiochemistrydiseasemanifestationandtherapy |