Synthesis of Sulfides and Persulfides Is Not Impeded by Disruption of Three Canonical Enzymes in Sulfur Metabolism
Reactive sulfur species, or persulfides and polysulfides, such as cysteine hydropersulfide and glutathione persulfide, are endogenously produced in abundance in both prokaryotes and eukaryotes, including mammals. Various forms of reactive persulfides occur in both low-molecular-weight and protein-bo...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-04-01
|
| Series: | Antioxidants |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3921/12/4/868 |
| _version_ | 1827746134910566400 |
|---|---|
| author | Qamarul Hafiz Zainol Abidin Tomoaki Ida Masanobu Morita Tetsuro Matsunaga Akira Nishimura Minkyung Jung Naim Hassan Tsuyoshi Takata Isao Ishii Warren Kruger Rui Wang Hozumi Motohashi Masato Tsutsui Takaaki Akaike |
| author_facet | Qamarul Hafiz Zainol Abidin Tomoaki Ida Masanobu Morita Tetsuro Matsunaga Akira Nishimura Minkyung Jung Naim Hassan Tsuyoshi Takata Isao Ishii Warren Kruger Rui Wang Hozumi Motohashi Masato Tsutsui Takaaki Akaike |
| author_sort | Qamarul Hafiz Zainol Abidin |
| collection | DOAJ |
| description | Reactive sulfur species, or persulfides and polysulfides, such as cysteine hydropersulfide and glutathione persulfide, are endogenously produced in abundance in both prokaryotes and eukaryotes, including mammals. Various forms of reactive persulfides occur in both low-molecular-weight and protein-bound thiols. The chemical properties and great supply of these molecular species suggest a pivotal role for reactive persulfides/polysulfides in different cellular regulatory processes (e.g., energy metabolism and redox signaling). We demonstrated earlier that cysteinyl-tRNA synthetase (CARS) is a new cysteine persulfide synthase (CPERS) and is responsible for the in vivo production of most reactive persulfides (polysulfides). Some researchers continue to suggest that 3-mercaptopyruvate sulfurtransferase (3-MST), cystathionine β-synthase (CBS), and cystathionine γ-lyase (CSE) may also produce hydrogen sulfide and persulfides that may be generated during the transfer of sulfur from 3-mercaptopyruvate to the cysteine residues of 3-MST or direct synthesis from cysteine by CBS/CSE, respectively. We thus used integrated sulfur metabolome analysis, which we recently developed, with 3-MST knockout (KO) mice and CBS/CSE/3-MST triple-KO mice, to elucidate the possible contribution of 3-MST, CBS, and CSE to the production of reactive persulfides in vivo. We therefore quantified various sulfide metabolites in organs derived from these mutant mice and their wild-type littermates via this sulfur metabolome, which clearly revealed no significant difference between mutant mice and wild-type mice in terms of reactive persulfide production. This result indicates that 3-MST, CBS, and CSE are not major sources of endogenous reactive persulfide production; rather, CARS/CPERS is the principal enzyme that is actually involved in and even primarily responsible for the biosynthesis of reactive persulfides and polysulfides in vivo in mammals. |
| first_indexed | 2024-03-11T05:18:17Z |
| format | Article |
| id | doaj.art-b737ee93d096493aa67c2beef592f38f |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-11T05:18:17Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-b737ee93d096493aa67c2beef592f38f2023-11-17T18:05:28ZengMDPI AGAntioxidants2076-39212023-04-0112486810.3390/antiox12040868Synthesis of Sulfides and Persulfides Is Not Impeded by Disruption of Three Canonical Enzymes in Sulfur MetabolismQamarul Hafiz Zainol Abidin0Tomoaki Ida1Masanobu Morita2Tetsuro Matsunaga3Akira Nishimura4Minkyung Jung5Naim Hassan6Tsuyoshi Takata7Isao Ishii8Warren Kruger9Rui Wang10Hozumi Motohashi11Masato Tsutsui12Takaaki Akaike13Department of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai 980-8575, JapanDepartment of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai 980-8575, JapanDepartment of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai 980-8575, JapanDepartment of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai 980-8575, JapanDepartment of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai 980-8575, JapanDepartment of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai 980-8575, JapanDepartment of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai 980-8575, JapanDepartment of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai 980-8575, JapanDepartment of Health Chemistry, Showa Pharmaceutical University, Machida, Tokyo 194-8543, JapanMolecular Therapeutics Program, Fox Chase Cancer Center, Philadelphia, PA 19111-2497, USAFaculty of Science, York University, Toronto, ON M3J 1P3, CanadaDepartment of Gene Expression Regulation, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, JapanDepartment of Pharmacology, Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0213, JapanDepartment of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai 980-8575, JapanReactive sulfur species, or persulfides and polysulfides, such as cysteine hydropersulfide and glutathione persulfide, are endogenously produced in abundance in both prokaryotes and eukaryotes, including mammals. Various forms of reactive persulfides occur in both low-molecular-weight and protein-bound thiols. The chemical properties and great supply of these molecular species suggest a pivotal role for reactive persulfides/polysulfides in different cellular regulatory processes (e.g., energy metabolism and redox signaling). We demonstrated earlier that cysteinyl-tRNA synthetase (CARS) is a new cysteine persulfide synthase (CPERS) and is responsible for the in vivo production of most reactive persulfides (polysulfides). Some researchers continue to suggest that 3-mercaptopyruvate sulfurtransferase (3-MST), cystathionine β-synthase (CBS), and cystathionine γ-lyase (CSE) may also produce hydrogen sulfide and persulfides that may be generated during the transfer of sulfur from 3-mercaptopyruvate to the cysteine residues of 3-MST or direct synthesis from cysteine by CBS/CSE, respectively. We thus used integrated sulfur metabolome analysis, which we recently developed, with 3-MST knockout (KO) mice and CBS/CSE/3-MST triple-KO mice, to elucidate the possible contribution of 3-MST, CBS, and CSE to the production of reactive persulfides in vivo. We therefore quantified various sulfide metabolites in organs derived from these mutant mice and their wild-type littermates via this sulfur metabolome, which clearly revealed no significant difference between mutant mice and wild-type mice in terms of reactive persulfide production. This result indicates that 3-MST, CBS, and CSE are not major sources of endogenous reactive persulfide production; rather, CARS/CPERS is the principal enzyme that is actually involved in and even primarily responsible for the biosynthesis of reactive persulfides and polysulfides in vivo in mammals.https://www.mdpi.com/2076-3921/12/4/868cystathionine β-synthasecystathionine γ-lyasecysteine persulfide synthasecysteinyl-tRNA synthetases3-mercaptopyruvate sulfurtransferasereactive persulfides/polysulfides |
| spellingShingle | Qamarul Hafiz Zainol Abidin Tomoaki Ida Masanobu Morita Tetsuro Matsunaga Akira Nishimura Minkyung Jung Naim Hassan Tsuyoshi Takata Isao Ishii Warren Kruger Rui Wang Hozumi Motohashi Masato Tsutsui Takaaki Akaike Synthesis of Sulfides and Persulfides Is Not Impeded by Disruption of Three Canonical Enzymes in Sulfur Metabolism Antioxidants cystathionine β-synthase cystathionine γ-lyase cysteine persulfide synthase cysteinyl-tRNA synthetases 3-mercaptopyruvate sulfurtransferase reactive persulfides/polysulfides |
| title | Synthesis of Sulfides and Persulfides Is Not Impeded by Disruption of Three Canonical Enzymes in Sulfur Metabolism |
| title_full | Synthesis of Sulfides and Persulfides Is Not Impeded by Disruption of Three Canonical Enzymes in Sulfur Metabolism |
| title_fullStr | Synthesis of Sulfides and Persulfides Is Not Impeded by Disruption of Three Canonical Enzymes in Sulfur Metabolism |
| title_full_unstemmed | Synthesis of Sulfides and Persulfides Is Not Impeded by Disruption of Three Canonical Enzymes in Sulfur Metabolism |
| title_short | Synthesis of Sulfides and Persulfides Is Not Impeded by Disruption of Three Canonical Enzymes in Sulfur Metabolism |
| title_sort | synthesis of sulfides and persulfides is not impeded by disruption of three canonical enzymes in sulfur metabolism |
| topic | cystathionine β-synthase cystathionine γ-lyase cysteine persulfide synthase cysteinyl-tRNA synthetases 3-mercaptopyruvate sulfurtransferase reactive persulfides/polysulfides |
| url | https://www.mdpi.com/2076-3921/12/4/868 |
| work_keys_str_mv | AT qamarulhafizzainolabidin synthesisofsulfidesandpersulfidesisnotimpededbydisruptionofthreecanonicalenzymesinsulfurmetabolism AT tomoakiida synthesisofsulfidesandpersulfidesisnotimpededbydisruptionofthreecanonicalenzymesinsulfurmetabolism AT masanobumorita synthesisofsulfidesandpersulfidesisnotimpededbydisruptionofthreecanonicalenzymesinsulfurmetabolism AT tetsuromatsunaga synthesisofsulfidesandpersulfidesisnotimpededbydisruptionofthreecanonicalenzymesinsulfurmetabolism AT akiranishimura synthesisofsulfidesandpersulfidesisnotimpededbydisruptionofthreecanonicalenzymesinsulfurmetabolism AT minkyungjung synthesisofsulfidesandpersulfidesisnotimpededbydisruptionofthreecanonicalenzymesinsulfurmetabolism AT naimhassan synthesisofsulfidesandpersulfidesisnotimpededbydisruptionofthreecanonicalenzymesinsulfurmetabolism AT tsuyoshitakata synthesisofsulfidesandpersulfidesisnotimpededbydisruptionofthreecanonicalenzymesinsulfurmetabolism AT isaoishii synthesisofsulfidesandpersulfidesisnotimpededbydisruptionofthreecanonicalenzymesinsulfurmetabolism AT warrenkruger synthesisofsulfidesandpersulfidesisnotimpededbydisruptionofthreecanonicalenzymesinsulfurmetabolism AT ruiwang synthesisofsulfidesandpersulfidesisnotimpededbydisruptionofthreecanonicalenzymesinsulfurmetabolism AT hozumimotohashi synthesisofsulfidesandpersulfidesisnotimpededbydisruptionofthreecanonicalenzymesinsulfurmetabolism AT masatotsutsui synthesisofsulfidesandpersulfidesisnotimpededbydisruptionofthreecanonicalenzymesinsulfurmetabolism AT takaakiakaike synthesisofsulfidesandpersulfidesisnotimpededbydisruptionofthreecanonicalenzymesinsulfurmetabolism |