Mapping the Metabolic Niche of Citrate Metabolism and <i>SLC13A5</i>
The small molecule citrate is a key molecule that is synthesized de novo and involved in diverse biochemical pathways influencing cell metabolism and function. Citrate is highly abundant in the circulation, and cells take up extracellular citrate via the sodium-dependent plasma membrane transporter...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | Metabolites |
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| Online Access: | https://www.mdpi.com/2218-1989/13/3/331 |
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| author | Fangfang Chen Hanna Friederike Willenbockel Thekla Cordes |
| author_facet | Fangfang Chen Hanna Friederike Willenbockel Thekla Cordes |
| author_sort | Fangfang Chen |
| collection | DOAJ |
| description | The small molecule citrate is a key molecule that is synthesized de novo and involved in diverse biochemical pathways influencing cell metabolism and function. Citrate is highly abundant in the circulation, and cells take up extracellular citrate via the sodium-dependent plasma membrane transporter NaCT encoded by the <i>SLC13A5</i> gene. Citrate is critical to maintaining metabolic homeostasis and impaired NaCT activity is implicated in metabolic disorders. Though citrate is one of the best known and most studied metabolites in humans, little is known about the consequences of altered citrate uptake and metabolism. Here, we review recent findings on <i>SLC13A5</i>, NaCT, and citrate metabolism and discuss the effects on metabolic homeostasis and <i>SLC13A5</i>-dependent phenotypes. We discuss the “multiple-hit theory” and how stress factors induce metabolic reprogramming that may synergize with impaired NaCT activity to alter cell fate and function. Furthermore, we underline how citrate metabolism and compartmentalization can be quantified by combining mass spectrometry and tracing approaches. We also discuss species-specific differences and potential therapeutic implications of <i>SLC13A5</i> and NaCT. Understanding the synergistic impact of multiple stress factors on citrate metabolism may help to decipher the disease mechanisms associated with SLC13A5 citrate transport disorders. |
| first_indexed | 2024-03-11T06:11:30Z |
| format | Article |
| id | doaj.art-a25e30bd38ca492cae39536fc3b36d8c |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-11T06:11:30Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-a25e30bd38ca492cae39536fc3b36d8c2023-11-17T12:36:00ZengMDPI AGMetabolites2218-19892023-02-0113333110.3390/metabo13030331Mapping the Metabolic Niche of Citrate Metabolism and <i>SLC13A5</i>Fangfang Chen0Hanna Friederike Willenbockel1Thekla Cordes2Research Group Cellular Metabolism in Infection, Helmholtz Centre for Infection Research (HZI), 38124 Braunschweig, GermanyDepartment of Bioinformatics and Biochemistry, Braunschweig Integrated Centre of Systems Biology (BRICS), Technische Universität Braunschweig, 38106 Braunschweig, GermanyResearch Group Cellular Metabolism in Infection, Helmholtz Centre for Infection Research (HZI), 38124 Braunschweig, GermanyThe small molecule citrate is a key molecule that is synthesized de novo and involved in diverse biochemical pathways influencing cell metabolism and function. Citrate is highly abundant in the circulation, and cells take up extracellular citrate via the sodium-dependent plasma membrane transporter NaCT encoded by the <i>SLC13A5</i> gene. Citrate is critical to maintaining metabolic homeostasis and impaired NaCT activity is implicated in metabolic disorders. Though citrate is one of the best known and most studied metabolites in humans, little is known about the consequences of altered citrate uptake and metabolism. Here, we review recent findings on <i>SLC13A5</i>, NaCT, and citrate metabolism and discuss the effects on metabolic homeostasis and <i>SLC13A5</i>-dependent phenotypes. We discuss the “multiple-hit theory” and how stress factors induce metabolic reprogramming that may synergize with impaired NaCT activity to alter cell fate and function. Furthermore, we underline how citrate metabolism and compartmentalization can be quantified by combining mass spectrometry and tracing approaches. We also discuss species-specific differences and potential therapeutic implications of <i>SLC13A5</i> and NaCT. Understanding the synergistic impact of multiple stress factors on citrate metabolism may help to decipher the disease mechanisms associated with SLC13A5 citrate transport disorders.https://www.mdpi.com/2218-1989/13/3/331SLC13A5NaCTcitrate metabolismmetabolic nichetracingmass spectrometry |
| spellingShingle | Fangfang Chen Hanna Friederike Willenbockel Thekla Cordes Mapping the Metabolic Niche of Citrate Metabolism and <i>SLC13A5</i> Metabolites SLC13A5 NaCT citrate metabolism metabolic niche tracing mass spectrometry |
| title | Mapping the Metabolic Niche of Citrate Metabolism and <i>SLC13A5</i> |
| title_full | Mapping the Metabolic Niche of Citrate Metabolism and <i>SLC13A5</i> |
| title_fullStr | Mapping the Metabolic Niche of Citrate Metabolism and <i>SLC13A5</i> |
| title_full_unstemmed | Mapping the Metabolic Niche of Citrate Metabolism and <i>SLC13A5</i> |
| title_short | Mapping the Metabolic Niche of Citrate Metabolism and <i>SLC13A5</i> |
| title_sort | mapping the metabolic niche of citrate metabolism and i slc13a5 i |
| topic | SLC13A5 NaCT citrate metabolism metabolic niche tracing mass spectrometry |
| url | https://www.mdpi.com/2218-1989/13/3/331 |
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