Specific Nature of Training on Skeletal Muscles
Atko Viru in Adaptation in Sports Training, 2017
Phosphofructokinase activity is controlled by AMP, ADP, ATP, citrate, ammonium, and fructose biphosphate.173 The enzyme is also sensitive to decrease in pH.174 The enzyme concentration itself may also modulate the activity: a cell with a high concentration of the enzyme will exhibit a higher activity than could be expected from the simple linear relationship between enzyme concentration and activity.175 It may be speculated that training-induced increase in the enzyme concentration sensitizes the enzyme activity to stimulatory factors. This explanation implies that the enzyme sensitivity to inhibitory factors is also increased. Thus, despite the elevated number of enzyme molecules, the activity was reduced in resting conditions. Final conclusion of the obtained results points to an enhanced effectiveness of the regulation of phosphofructokinase activity in the organism trained by interval or continuous exercises.
Anaerobic endurance: the speed endurance sports
Nick Draper, Helen Marshall in Exercise Physiology, 2014
As the catalyst for the third step in the glycolytic pathway, phosphofructokinase activity is increased with the accumulation of its substrate, fructose-6-phosphate. In addition, a range of metabolites are involved in its control. At rest, skeletal muscle contains higher concentrations of ATP and PCr, while levels of ADP, AMP, Pi and are low. In this situation, PFK activity is inhibited by the high ATP and PCr concentrations. Additionally, H+ enhance the inhibition by ATP, and citrate, found in the cytoplasm when aerobic metabolism is meeting the energy demands (refer to Chapter 12 for further detail), acts as an inhibitor of PFK.
The Bioenergetics of Mammalian Sperm Motility
Claude Gagnon in Controls of Sperm Motility, 2020
About 50% of the fructose 1,6-bisphosphate produced by phosphofructokinase is recycled to fructose 6-phosphate and this is nearly independent of glycolytic flux. At low glycolytic flux, substrate cycling consumes all or nearly all the ATP produced by the conversion of glucose to lactate and the pathway probably serves as source of pyruvate for mitochondrial respiration. Futile substrate cycling also occurs in boar and rat spermatozoa. In the boar, increased cycling of hexose phosphates accounts for a large part of the decrease in net glycolytic flux when pyruvate and lactate are added to the incubation.6
PFKFB3 downregulation aggravates Angiotensin II-induced podocyte detachment
Published in Renal Failure, 2023
Xiaoxiao Huang, Zhaowei Chen, Zilv Luo, Yiqun Hao, Jun Feng, Zijing Zhu, Xueyan Yang, Zongwei Zhang, Jijia Hu, Wei Liang, Guohua Ding
The homodimeric and bifunctional enzyme family of phosphofructokinase-2/Fructose-2,6-bisphosphatase (PFK-2/PFKFB) promotes glycolysis by increasing levels of fructose-2,6-bisphosphate (F2,6P2), which in turn activates the key rate-limiting enzyme 6-phosphofructo-1-kinase (PFK-1) and enhances the conversion of fructose-6-phosphate (F6P) to fructose-1,6-bisphosphate (F1,6P2) in the glycolytic pathway. This causes increased glycolytic flux and increased ATP and NADH production [16]. Among the PFKFB family of four enzymes (PFKFB1-4), PFKFB3 has the highest ratio of kinase to phosphatase activity, which ensures a high glycolytic rate [17]. Recent findings have indicated that PFKFB3 exerts protective effects on the kidneys [18] and promotes the activation of cyclin-dependent kinase-1(cdk1) [19], which promotes talin1 phosphorylation [20]. Excessive talin1 phosphorylation promotes integrin beta1 subunit (ITGB1) activity on the cell surface [21]. Active ITGB1 is an important adhesion molecule on the surface of podocytes, and its activation enhances podocyte adhesion capacity [22–25]. Inhibiting PFKFB3 significantly reduces the expression of cell adhesion molecules, resulting in diminished cell adhesion [26–29]. Therefore, we speculated that Ang II could inhibit talin1 phosphorylation and ITGB1 activation through downregulating PFKFB3 expression. Therefore, we investigated the role of PFKFB3 in Ang II-induced podocyte injury and identified a novel target for CKD treatment.
Glucose metabolism inhibitor PFK-015 combined with immune checkpoint inhibitor is an effective treatment regimen in cancer
Published in OncoImmunology, 2022
Jia Bo Zheng, Chau Wei Wong, Jia Liu, Xiao-Jing Luo, Wei-Yi Zhou, Yan-Xing Chen, Hui-Yan Luo, Zhao-Lei Zeng, Chao Ren, Xiao-Ming Xie, De-Shen Wang
Glycolysis intensity is regulated by the activity of three physiologically reversible enzymes: hexokinase, phosphofructokinase-1 (PFK-1), and pyruvate kinase. PFK-1 is the main rate-limiting enzyme of glycolysis and the activity of PFK-1 is regulated by metabolic products such as adenosine triphosphate (ATP), adenosine diphosphate (ADP), and fructose 2–6 biphosphate.4 Of these compounds, F-2-6-BP is a reaction product catalyzed by 6-phosphofructose 2-kinase/fructose-2,6-biphosphatase (PFK-2/FBPase-2/PFKFB), which is also the most potent positive allosteric effector of PFK-1.4,5 PFKFB is a bifunctional enzyme responsible for the catalyzation of both the synthesis and degradation of F-2,6-BP mediated through its N-terminal domain (2-kase) and C-terminal domain (2-pase) respectively. Of note, the active site of the 2-kase domain has 2 distinct key areas (the F-6-P binding loop and the ATP-binding loop) which are essential for PFKFB to function.6
Microglia as therapeutic targets after neurological injury: strategy for cell therapy
Published in Expert Opinion on Therapeutic Targets, 2021
M. Collins Scott, Supinder S. Bedi, Scott D. Olson, Candice M. Sears, Charles S. Cox
When stimulated by an inflammatory insult, microglia uses anaerobic metabolism, in particular glycolysis, for rapid energy production. Gimeno-Bayón et al. performed in vitro analysis of BV-2 microglia by inducing the M1 inflammatory state with lipopolysaccharides (LPS) and IFN-γ. After stimulation, the BV-2 cells increased glucose consumption, hexokinase activity, and lactate production. While there was no change in the inner membrane potential of mitochondria, the glucose:lactate ratio increased, indicating a shift to anaerobic metabolism by BV-2 microglia [70]. Holland et al obtained similar results in mice when stimulating microglia with IFN-γ; they also demonstrated that expression of the isozyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKB3) increased in microglia after IFN-γ stimulation. PFKB3 is an important allosteric activator of phosphofructokinase-1, the rate-limiting enzyme of glycolysis [71]. To cope with the increased glucose demand, BV-2 microglia will increase expression of glucose-uptake membrane transporters (GLUT), in particular, GLUT1 and GLUT4 [70,72]. Microglia increase GLUT expression in response to increased glucose requirements in the M1 state. Inhibition of glycolysis can attenuate the pro-inflammatory response of stimulated microglia. In vitro studies have demonstrated this with 2-deoxy-D-glucose (2-DG), a glycolytic inhibitor. 2-DG treatment decreases microglial secretion of certain inflammatory cytokines in mice, like TNF-α, IL-1β, and IL-6 [73,74]
Related Knowledge Centers
- Adenosine Monophosphate
- Allosteric Regulation
- Tetrameric Protein
- Phosphorylation
- Glycolysis
- Kinase
- Fructose 6-Phosphate
- Phosphoryl Group
- Adenosine Triphosphate
- Fructose 1,6-Bisphosphate