Epithelial Mesenchymal Transition Induces Aberrant Glycosylation through Hexosamine Biosynthetic Pathway Activation.

Deregulated cellular metabolism is a hallmark of tumors. Cancer cells increase glucose and glutamine flux to provide energy needs and macromolecular synthesis demands. Several studies have been focused on the importance of glycolysis and pentose phosphate pathway.

Exogenous citrate impairs glucose tolerance and promotes visceral adipose tissue inflammation in mice.

Overweight and obesity have become epidemic worldwide and are linked to sedentary lifestyle and the consumption of processed foods and drinks. Citrate is a metabolite that plays central roles in carbohydrate and lipid metabolism. In addition, citrate is the additive most commonly used by the food industry, and therefore is highly consumed.

Serotonin modulates hepatic 6-phosphofructo-1-kinase in an insulin synergistic manner.

Human and rat hepatic tissue express many serotonin (5-HT) receptor subtypes, such as 5-HT(1B), 5-HT(2A), 5-HT(2B) and 5-HT(7) receptors, which mediate diverse effects. 5-HT is known to regulate several key aspects of liver biology including hepatic blood flow, innervations and wound healing. 5-HT is also known to enhance net glucose uptake during glucose infusion in fasted dogs, but little is known about the ability of 5-HT to control hepatic glucose metabolism, especially glycolysis.

Regulation of mammalian muscle type 6-phosphofructo-1-kinase and its implication for the control of the metabolism.

Phosphofructokinase (PFK) is a major regulatory glycolytic enzyme and is considered to be the pacemaker of glycolysis. This enzyme presents a puzzling regulatory mechanism that is modulated by a large variety of metabolites, drugs, and intracellular proteins. To date, the mammalian enzyme structure has not yet been resolved.

Lactate downregulates the glycolytic enzymes hexokinase and phosphofructokinase in diverse tissues from mice.

We examined the effects of lactate on the enzymatic activity of hexokinase (HK), phosphofructokinase (PFK) and pyruvate kinase (PK) in various mouse tissues. Our results showed that lactate inhibited PFK activity in all the analyzed tissues. This inhibitory effect was observed in skeletal muscle even in the presence of insulin.

Calmodulin upregulates skeletal muscle 6-phosphofructo-1-kinase reversing the inhibitory effects of allosteric modulators.

6-phosphofructo-1-kinase (PFK) is a calmodulin (CaM)-binding protein that plays a key role on the regulation of glycolysis. Each PFK monomer binds two CaM molecules inducing the dissociation of the active tetrameric conformation of the enzyme into dimers, thus inhibiting it. Recently, we have reported that the binding of one CaM per PFK monomer promotes the dimerization of the enzyme although maintaining its full catalytic activity.

ATP and fructose-2,6-bisphosphate regulate skeletal muscle 6-phosphofructo-1-kinase by altering its quaternary structure.

Recently, it has been demonstrated that fructose-2,6-bisphosphate (F2,6BP) protects skeletal muscle 6-phosphofructo-1-kinase (PFK) from thermal inactivation (50 degrees C) and against the deleterious effects of guanidinium hydrochloride (GdmCl). On the other hand, ATP, when added at its inhibitory concentrations, that is, >1 mM, enhanced either the thermal- or GdmCl-induced inactivation of PFK. Moreover, we concluded that these phenomena were probably due to the stabilization of PFK tetrameric structure by F2,6BP, and the dissociation of this structure into dimers induced by ATP.

Allosteric regulation of 6-phosphofructo-1-kinase activity of fat body and flight muscle from the bloodsucking bug Rhodnius prolixus.

6-Phosphofructo-1-kinase (phosphofructokinase; PFK) activity from Rhodnius prolixus, a haematophagous insect which is usually a poor flyer, was measured and compared in two metabolically active tissues - flight muscle and fat body. The activity of this important regulatory glycolytic enzyme was much more pronounced in muscle (15.1 +/- 1.

Clotrimazole inhibits and modulates heterologous association of the key glycolytic enzyme 6-phosphofructo-1-kinase.

Clotrimazole is an antifungal azole derivative recently recognized as a calmodulin antagonist with promising anticancer effects. This property has been correlated with the ability of the drug to decrease the viability of tumor cells by inhibiting their glycolytic flux and consequently decreasing the intracellular concentration of ATP. The effects of clotrimazole on cell glycolysis and ATP production are considered to be due to the detachment of the glycolytic enzymes from the cytoskeleton.

Modulation of 6-phosphofructo-1-kinase oligomeric equilibrium by calmodulin: formation of active dimers.

Muscle 6-phospho-1-kinase (PFK) is the key regulatory enzyme of the glycolytic pathway and is a calmodulin-binding protein binding two calmodulin molecules per PFK protomer. This enzyme is characterized by a complex regulation that involves its allosteric behavior modulated by several ligands, which modulate the equilibrium between the active tetramers and the inactive dimers of the enzyme. Calmodulin is described to induce the dimerization of PFK, so inhibiting its catalytic activity.

Clotrimazole decreases human breast cancer cells viability through alterations in cytoskeleton-associated glycolytic enzymes.

Cancer cells are characterized by a high rate of glycolysis, which is their primary energy source. Glycolysis is known to be controlled by allosteric regulators, as well as by reversible binding of glycolytic enzymes to cytoskeleton. Clotrimazole is an anti-fungal azole derivative recently recognized as a calmodulin antagonist with promising anti-cancer effect.