Journal of Energy Bioscience 2025, Vol.16, No.1, 21-30 http://bioscipublisher.com/index.php/jeb 25 5 Mechanisms Regulating ATP Production and Utilization 5.1 Allosteric regulation of key enzymes (such as ATP synthase) When cells make ATP, some key enzymes are "allosterically regulated", which is a way to regulate enzyme activity. ATP synthase is one of the most important enzymes. IF1 (an inhibitor) can inhibit its activity in certain cases, thereby preventing unnecessary ATP from being wasted (Domínguez-Zorita et al., 2022) (Figure 3). In F-type ATP synthase, ADP and ATP also regulate the efficiency of the enzyme, keeping the ratio of H+ and ATP generation reasonable, which helps maintain the energy balance of the cell (Turina, 2022). In the glycolysis process, pyruvate kinase is an important enzyme. Its activity will change due to different small molecules, thus helping cells adjust the metabolic rate according to actual needs (Schormann et al., 2019). There is also AMPK (AMP-activated protein kinase), which is activated by AMP or ADP when the cell is short of energy, allowing the cell to start producing more ATP (Matos et al., 2019). Figure 3 IF1 is tissue-specifically expressed and plays a central role in neuronal function and learning (Adopted from Domínguez-Zorita et al., 2022) Image caption: (A) The ratio of IF1 to ATP synthase varies across tissues and between humans and mice, with the highest expression observed in specific organs. (B) IF1 binding to ATP synthase is reversible and regulated by phosphorylation, which limits its availability for binding, and potentially by rapid degradation through proteases. (C) IF1 binding promotes ATP synthase tetramer formation, increasing proton-motive force and mitochondrial ROS production. (D) In hippocampal neurons, IF1 helps organize mitochondrial cristae and modulate oxidative phosphorylation, contributing to synaptic transmission and learning through mtROS-activated signaling pathways like ERK 1/2 (Adapted from Domínguez-Zorita et al., 2022) 5.2 Feedback mechanisms in metabolic pathways (such as ADP/ATP ratio) Cells use a method called "feedback regulation" to control ATP production. This method adjusts enzyme activity according to the ratio of ADP to ATP to keep energy balanced. In mitochondria, there is an enzyme called cytochrome c oxidase (COX). It will be inhibited when there is a lot of ATP, so that the mitochondrial membrane potential will not be too high, while reducing the generation of harmful reactive oxygen species (ROS) and protecting cells from damage (Kadenbach, 2020). When the ADP concentration is high, it will relieve the inhibition of ATP synthase and help cells replenish ATP quickly (Turina, 2022). In glycolysis, ADP and ATP can also regulate the activity of pyruvate kinase, allowing the entire process to operate flexibly according to energy needs (Schormann et al., 2019).
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