Journal of Energy Bioscience 2025, Vol.16, No.1, 42-52 http://bioscipublisher.com/index.php/jeb 43 2 Biochemical Basis of the Creatine Phosphate System 2.1 Structure and function of creatine and phosphocreatine Creatine (Cr) is a small molecule that the body can synthesize by itself, mainly in the liver, kidneys and pancreas. It relies on a special transporter protein to enter the cell, which requires sodium and chloride to work, called creatine transporter (CRT) (Bonilla et al., 2021a). Once creatine enters the cell, it will be converted into creatine phosphate (Phosphocreatine, PCr) under the action of creatine kinase (CK). This process is reversible, that is, it can be converted back and forth. This conversion is very useful for cells to maintain energy stability, especially those tissues with high energy consumption and rapid changes, such as skeletal muscle, heart, neurons and photoreceptor cells of the eye (Wallimann et al., 1998; Wallimann et al., 2011). PCr is like a "small energy warehouse". When the cell suddenly needs a lot of energy, it can immediately help ADP regenerate ATP. This is particularly important for muscle cells, because PCr helps keep ATP from dropping when muscle contraction begins (Greenhaff, 2001). In addition, the CK/PCr system can also transfer energy from mitochondria (where ATP is produced) to places such as myofibrils where ATP is actually consumed, a process called "phosphocreatine shuttling" (Greenhaff, 2001; Wallimann et al., 2011). 2.2 Enzymatic mechanisms of creatine kinase in ATP regeneration Creatine kinase (CK) catalyzes an important reaction: it transfers a phosphorus group from ATP to creatine, thus generating ADP and PCr. This reaction is reversible, and for cells with particularly active energy metabolism, this process helps maintain ATP levels. There are several different types of CK. Some of them are found in the cytoplasm (such as MM-CK, MB-CK, BB-CK), while others are found in the mitochondria (Mi-CK). These different forms are cleverly distributed throughout the cell, helping to transfer energy from where it is generated to where it is used (Wallimann et al., 1998; McLeish and Kenyon, 2005). CK works in a linear manner, that is, it transfers the phosphorus group from ATP to creatine step by step. Its active site helps this reaction proceed smoothly. Researchers have seen the intermediate state of this reaction through methods such as X-ray crystallography, which also verifies some of the speculations from previous kinetic and mutation experiments (McLeish and Kenyon, 2005). In mitochondria, CK is often close to a transporter protein called ANT. This position is very critical because it allows the generation of ATP and the synthesis of PCr to be directly connected, thereby helping the cell buffer energy changes and maintain ATP levels in the cytoplasm (Jacobus, 1985; Guzun et al., 2011). 2.3 Comparison of creatine phosphate with other energy storage systems The creatine phosphate system has a great advantage that it can regenerate ATP very quickly. This feature is particularly important for tissues that often require a large amount of energy suddenly, such as muscles during exercise. In contrast, energy storage methods such as glycogen or fat can provide more energy, but the release rate is not as fast (Greenhaff, 2001; Wallimann et al., 2011). Glycogen can provide energy continuously, but it is relatively slow to mobilize. To generate ATP from glycogen, many steps are required. Glycogen must first be converted into glucose-6-phosphate and then further produce ATP, which is not timely enough for the sudden increase in energy demand in a short period of time (Greenhaff, 2001). Similarly, triglycerides in adipose tissue can provide energy for a long time, but they also need to be lipolyzed and β-oxidized, which is a relatively slow process. This makes it not respond quickly enough when high-intensity and rapid energy use is required (Wallimann et al., 2011). 3 Molecular Mechanisms of Creatine Phosphate in Energy Storage and Release 3.1 Steps involved in phosphocreatine synthesis and breakdown The generation and decomposition of creatine phosphate (PCr) is an important step in cellular energy management. First, creatine (Cr) is transported into the cell through a sodium/chloride-dependent transporter (CRT) (Bonilla et al., 2021a) (Figure 1). After creatine enters the cell, creatine kinase (CK) helps it get a phosphate group from ATP, thus turning it into PCr and generating ADP at the same time. This reaction is reversible, in other words, PCr can also turn back into creatine and release ATP. This process is particularly critical in tissues such as muscles and
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