Sulfide regulation and catabolism in health and disease
Abstract The metabolic pathway of sulfur-containing amino acids in organisms begins with methionine, which is metabolized to produce important sulfur-containing biomolecules such as adenosylmethionine, adenosylhomocysteine, homocysteine, cystine, and hydrogen sulfide (H2S). These sulfur-containing b...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2025-05-01
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| Series: | Signal Transduction and Targeted Therapy |
| Online Access: | https://doi.org/10.1038/s41392-025-02231-w |
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| Summary: | Abstract The metabolic pathway of sulfur-containing amino acids in organisms begins with methionine, which is metabolized to produce important sulfur-containing biomolecules such as adenosylmethionine, adenosylhomocysteine, homocysteine, cystine, and hydrogen sulfide (H2S). These sulfur-containing biomolecules play a wide range of physiological roles in the body, including anti-inflammation, antioxidant stress, DNA methylation, protein synthesis, etc., which are essential for maintaining cellular function and overall health. In contrast, dysregulation of the metabolic pathway of sulfur-containing amino acids leads to abnormal levels of sulfur-containing biomolecules, which produce a range of pathological consequences in multiple systems of the body, such as neurodegenerative diseases, cardiovascular diseases, and cancer. This review traces the milestones in the development of these sulfur-containing biomolecules from their initial discovery to their clinical applications and describes in detail the structure, physiochemical properties, metabolism, sulfide signaling pathway, physiopathological functions, and assays of sulfur-containing biomolecules. In addition, the paper also explores the regulatory role and mechanism of sulfur-containing biomolecules on cardiovascular diseases, liver diseases, neurological diseases, metabolic diseases and tumors. The focus is placed on donors of sulfur-containing biological macromolecule metabolites, small-molecule drug screening targeting H2S-producing enzymes, and the latest advancements in preclinical and clinical research related to hydrogen sulfide, including clinical trials and FDA-approved drugs. Additionally, an overview of future research directions in this field is provided. The aim is to enhance the understanding of the complex physiological and pathological roles of sulfur-containing biomolecules and to offer insights into developing effective therapeutic strategies for diseases associated with dysregulated sulfur-containing amino acid metabolism. |
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| ISSN: | 2059-3635 |