Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.3 (phospholipase C)
 18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Macrophages can adapt to the absence of oxygen by switching to anaerobic glycolysis. In this study, we investigated (a) the roles of fructose 2,6-bisphosphate (Fru-2,6-P2) and ribose 1,5-bisphosphate (Rib-1,5-P2), potent activators of phosphofructokinase, (b) the enzymes responsible for the synthesis of Rib-1,5-P2, and (c) the mechanisms of regulation of these enzymes in H36.12j macrophages during the initial phase of hypoxia. Within 1 min after initiating hypoxia, glycolysis was activated through activation of phosphofructokinase. Over the same period, Fru-2,6-P2 decreased 50% and recovered completely upon reoxygenation. Similar changes in cAMP levels were observed. In contrast, the Rib-1,5-P2 concentration rapidly increased to a maximum level of 8.0 +/- 0.9 nmol/g cell 30 s after hypoxia. Thus, Rib-1,5-P2 was the major factor increasing the rate of glycolysis during the initial phase of hypoxia. Moreover, we found that Rib-1,5-P2 was synthesized by two steps: the ribose-phosphate pyrophosphokinase (5-phosphoribosyl-1-pyrophosphate synthetase; PRPP synthetase) reaction (EC ) catalyzing the reaction, Rib-5-P + ATP --> PRPP + AMP and a new enzyme, "PRPP pyrophosphatase" catalyzing the reaction, PRPP --> Rib-1,5-P2 + P(i). Both PRPP synthetase and PRPP pyrophosphatase were significantly activated 30 s after hypoxia. Pretreatment with 1-octadecyl-2-methyl-rac-glycero-3-phosphocholine and calphostin C prevented the activation of ribose PRPP synthetase and PRPP pyrophosphatase as well as increase in Rib-1,5-P2 and activation of phosphofructokinase 30 s after hypoxia. These data suggest that the activation of the above enzymes was mediated by protein kinase C acting via activation of phosphatidylinositol specific phospholipase C in the macrophages during hypoxia.
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PMID:Regulation of energy metabolism in macrophages during hypoxia. Roles of fructose 2,6-bisphosphate and ribose 1,5-bisphosphate. 1137 80

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. This study addresses the potential of 5-HT to regulate PFK activity and the mechanisms related to the enzyme activity. Based on our results, we are the first to provide evidence that 5-HT up-regulates PFK in mouse hepatic tissue. Activation of the enzyme occurs through the 5-HT(2A) receptor and phospholipase C (PLC), resulting in PFK intracellular redistribution and favoring PFK association to the cytoskeletal f-actin-enriched fractions. Interestingly, 5-HT and insulin act in a synergistic manner, likely because of the ability of insulin to increase fructose-2,6-bisphosphate because the presence of this PFK allosteric regulator enhances the 5-HT effect on the enzyme activity. Together, these data demonstrate the ability of 5-HT to control hepatic glycolysis and present clues about the mechanisms involved in these processes, which may be important in understanding the action of 5-HT during the hepatic wound healing process.
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PMID:Serotonin modulates hepatic 6-phosphofructo-1-kinase in an insulin synergistic manner. 2203 24