Phosphoenolpyruvate carboxykinase in cell metabolism: Roles and mechanisms beyond gluconeogenesis
Background: Phosphoenolpyruvate carboxykinase (PCK) has been almost exclusively recognized as a critical enzyme in gluconeogenesis, especially in the liver and kidney. Accumulating evidence has shown that the enhanced activity of PCK leads to increased glucose output and exacerbation of diabetes, wh...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-11-01
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| Series: | Molecular Metabolism |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2212877821001022 |
| _version_ | 1819041805350469632 |
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| author | Shuo Yu Simin Meng Meixiang Xiang Hong Ma |
| author_facet | Shuo Yu Simin Meng Meixiang Xiang Hong Ma |
| author_sort | Shuo Yu |
| collection | DOAJ |
| description | Background: Phosphoenolpyruvate carboxykinase (PCK) has been almost exclusively recognized as a critical enzyme in gluconeogenesis, especially in the liver and kidney. Accumulating evidence has shown that the enhanced activity of PCK leads to increased glucose output and exacerbation of diabetes, whereas the defects of PCK result in lethal hypoglycemia. Genetic mutations or polymorphisms are reported to be related to the onset and progression of diabetes in humans. Scope of review: Recent studies revealed that the PCK pathway is more complex than just gluconeogenesis, depending on the health or disease condition. Dysregulation of PCK may contribute to the development of obesity, cardiac hypertrophy, stroke, and cancer. Moreover, a regulatory network with multiple layers, from epigenetic regulation, transcription regulation, to posttranscription regulation, precisely tunes the expression of PCK. Deciphering the molecular basis that regulates PCK may pave the way for developing practical strategies to treat metabolic dysfunction. Major conclusions: In this review, we summarize the metabolic and non-metabolic roles of the PCK enzyme in cells, especially beyond gluconeogenesis. We highlight the distinct functions of PCK isoforms (PCK1 and PCK2), depict a detailed network regulating PCK's expression, and discuss its clinical relevance. We also discuss the therapeutic potential targeting PCK and the future direction that is highly in need to better understand PCK-mediated signaling under diverse conditions. |
| first_indexed | 2024-12-21T09:30:50Z |
| format | Article |
| id | doaj.art-bbf18c88c61a4404a1cc0aabbd27c30d |
| institution | Directory Open Access Journal |
| issn | 2212-8778 |
| language | English |
| last_indexed | 2024-12-21T09:30:50Z |
| publishDate | 2021-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Metabolism |
| spelling | doaj.art-bbf18c88c61a4404a1cc0aabbd27c30d2022-12-21T19:08:45ZengElsevierMolecular Metabolism2212-87782021-11-0153101257Phosphoenolpyruvate carboxykinase in cell metabolism: Roles and mechanisms beyond gluconeogenesisShuo Yu0Simin Meng1Meixiang Xiang2Hong Ma3Anesthesiology Department, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310009, ChinaDepartment of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310009, ChinaDepartment of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310009, China; Corresponding author. 88 Jiefang Road, Hangzhou, Zhejiang, 310009, China.Department of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310009, China; Corresponding author. 88 Jiefang Road, Hangzhou, Zhejiang, 310009, China.Background: Phosphoenolpyruvate carboxykinase (PCK) has been almost exclusively recognized as a critical enzyme in gluconeogenesis, especially in the liver and kidney. Accumulating evidence has shown that the enhanced activity of PCK leads to increased glucose output and exacerbation of diabetes, whereas the defects of PCK result in lethal hypoglycemia. Genetic mutations or polymorphisms are reported to be related to the onset and progression of diabetes in humans. Scope of review: Recent studies revealed that the PCK pathway is more complex than just gluconeogenesis, depending on the health or disease condition. Dysregulation of PCK may contribute to the development of obesity, cardiac hypertrophy, stroke, and cancer. Moreover, a regulatory network with multiple layers, from epigenetic regulation, transcription regulation, to posttranscription regulation, precisely tunes the expression of PCK. Deciphering the molecular basis that regulates PCK may pave the way for developing practical strategies to treat metabolic dysfunction. Major conclusions: In this review, we summarize the metabolic and non-metabolic roles of the PCK enzyme in cells, especially beyond gluconeogenesis. We highlight the distinct functions of PCK isoforms (PCK1 and PCK2), depict a detailed network regulating PCK's expression, and discuss its clinical relevance. We also discuss the therapeutic potential targeting PCK and the future direction that is highly in need to better understand PCK-mediated signaling under diverse conditions.http://www.sciencedirect.com/science/article/pii/S2212877821001022Phosphoenolpyruvate carboxykinase (PCK)GluconeogenesisGlyceroneogenesisTranscription regulationPosttranscription regulationEpigenetic regulation |
| spellingShingle | Shuo Yu Simin Meng Meixiang Xiang Hong Ma Phosphoenolpyruvate carboxykinase in cell metabolism: Roles and mechanisms beyond gluconeogenesis Molecular Metabolism Phosphoenolpyruvate carboxykinase (PCK) Gluconeogenesis Glyceroneogenesis Transcription regulation Posttranscription regulation Epigenetic regulation |
| title | Phosphoenolpyruvate carboxykinase in cell metabolism: Roles and mechanisms beyond gluconeogenesis |
| title_full | Phosphoenolpyruvate carboxykinase in cell metabolism: Roles and mechanisms beyond gluconeogenesis |
| title_fullStr | Phosphoenolpyruvate carboxykinase in cell metabolism: Roles and mechanisms beyond gluconeogenesis |
| title_full_unstemmed | Phosphoenolpyruvate carboxykinase in cell metabolism: Roles and mechanisms beyond gluconeogenesis |
| title_short | Phosphoenolpyruvate carboxykinase in cell metabolism: Roles and mechanisms beyond gluconeogenesis |
| title_sort | phosphoenolpyruvate carboxykinase in cell metabolism roles and mechanisms beyond gluconeogenesis |
| topic | Phosphoenolpyruvate carboxykinase (PCK) Gluconeogenesis Glyceroneogenesis Transcription regulation Posttranscription regulation Epigenetic regulation |
| url | http://www.sciencedirect.com/science/article/pii/S2212877821001022 |
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