[HTML][HTML] Phosphoenolpyruvate carboxykinase in cell metabolism: Roles and mechanisms beyond gluconeogenesis

S Yu, S Meng, M Xiang, H Ma - Molecular metabolism, 2021 - Elsevier
S Yu, S Meng, M Xiang, H Ma
Molecular metabolism, 2021Elsevier
Abstract Background Phosphoenolpyruvate Carboxykinase (PCK) has been almost
exclusively recognized as a critical enzyme in gluconeogenesis, especially in liver and
kidney. Accumulating evidence has already shown that the enhanced activity of PCK leads
to increased glucose output and exacerbation of diabetes, whereas the defect of PCK results
in lethal hypoglycemia. Genetic mutation or polymorphism is reported to be related with the
onset and progression of diabetes in human. Scope of review However, latest studies reveal …
Background
Phosphoenolpyruvate Carboxykinase (PCK) has been almost exclusively recognized as a critical enzyme in gluconeogenesis, especially in liver and kidney. Accumulating evidence has already shown that the enhanced activity of PCK leads to increased glucose output and exacerbation of diabetes, whereas the defect of PCK results in lethal hypoglycemia. Genetic mutation or polymorphism is reported to be related with the onset and progression of diabetes in human.
Scope of review
However, latest studies reveal that 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 etc. 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 the development of practical strategies to treat metabolic dysfunction.
Major conclusions
In this review, we summarize the metabolic and non-metabolic roles of PCK enzyme in cells especially beyond gluconeogenesis. We highlight the distinct functions of PCK isoforms (PCK1 and PCK2), depict a detailed network regulating PCK 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.
Elsevier