Journal of Energy Bioscience 2025, Vol.16, No.1, 42-52 http://bioscipublisher.com/index.php/jeb 49 7.3 Recent breakthroughs in understanding the creatine phosphate system Recent studies have brought many new discoveries. The creatine phosphate system not only has an energy storage function, but also helps cells maintain balance and protect cells. The CK/PCr system is like an "energy sensor" and plays an important role in the survival, growth and movement of cells (Bonilla et al., 2021a). Tachikawa et al. (2004) found in their research that the distribution of creatine synthase and CK in the brain is very special. They are expressed differently in different types of cells. There may be an energy cooperation relationship between glial cells and neurons. After glial cells synthesize creatine, they may transport it to neurons for use. Creatine is not only active in normal physiological processes, but also plays a certain therapeutic role in diseases such as ischemia or inflammation (Kitzenberg et al., 2016). 8 Future Perspectives and Potential Research Directions 8.1 Unresolved questions regarding molecular regulation and system integration Although much progress has been made in the study and understanding of the phosphocreatine (PCr) system, there are still many questions that need to be answered. One of the important questions is how creatine transport is regulated and how it cooperates with the cell's energy system. Current research results have not yet involved the specific process of how creatine transporter (CRT-1) works with substrates and ions in different body states, and how creatine transporter maintains creatine concentration in cells (Farr et al., 2022). The specific distribution of creatine kinase (CK) and PCr in cells, as well as their respective roles in cellular energy regulation, also require researchers to conduct more research (Puurand et al., 2018; Bonilla et al., 2021a). Another question is: In addition to creatine kinase, are there other proteins involved in PCr metabolism? For this question, there are only some indirect clues (Kazak and Spiegelman, 2020). If we can understand these mechanisms, we can further understand why various diseases occur when creatine metabolism goes wrong (Kazak and Cohen, 2020; Bonilla et al., 2021a). 8.2 Prospects of creatine-based therapies and enhancement of energy systems Current studies have shown that creatine supplementation may help many health problems, such as improving the energy system, alleviating neurodegenerative diseases, metabolic abnormalities, and even cardiovascular diseases (Clarke et al., 2020). The mechanism of how creatine exerts these effects is not fully understood. Future studies need to focus on the relationship between dose and effect, and further explore the molecular pathways through which it works, such as whether certain kinases or ubiquitin-related mechanisms are involved (Bonilla et al., 2021b). Whether creatine can improve vascular function and whether it has antioxidant or anti-inflammatory effects are also worth further study (Clarke et al., 2020). These issues need to be verified through high-quality clinical studies. In particular, more large-scale multicenter randomized controlled trials (RCTs) are needed to determine whether creatine treatment is really effective and safe in the long term (Hao et al., 2021). 8.3 Integration of creatine phosphate metabolism with other metabolic pathways The relationship between creatine phosphate and other metabolic pathways is a promising research direction. It is not clear how the CK/PCr system interacts with oxidative phosphorylation (OXPHOS) in cells, and how they work together to help cells maintain energy balance in different tissues (Puurand et al., 2018). Whether creatine affects thermogenic respiration and overall energy expenditure in adipose tissue is also a topic that needs further study (Kazak and Cohen, 2020; Kazak and Spiegelman, 2020). Whether there is a connection between creatine metabolism and glucose metabolism is also a question worthy of attention. Some studies have found that in creatine transporter-deficient models, the expression of glucose transporters has changed, and even the efficiency of glucose clearance has increased (Stockebrand et al., 2018). Understanding these mechanisms will be of great help in finding new ways to treat metabolic diseases and energy-related diseases in the future. 9 Conclusion The creatine phosphate system is an important mechanism for maintaining cellular energy balance, especially in high-energy-consuming tissues such as muscles and the brain. Creatine kinase (CK) can catalyze the reversible reaction between creatine and ATP to generate creatine phosphate (PCr) and ADP. PCr is like an "energy backup
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