Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is a positive correlation between lactate output and insulin secretion but there is no correlation between total islet PEP content and insulin secretion and no correlation between cAMP production and insulin release. Neither PEP or cAMP seem to be primary triggers to insulin release but may rather act as positive modulators of insulin secretion. Potentially, PEP can maintain an elevated cytoplasmic Ca++ concentration by inhibiting Ca++ uptake in the mitochondria, increase the concentration of cAMP in the beta-cells by activating the adenylate cyclase (11) and change the phosphorylation state of the plasma membrane (12). The possible trigger effect of an increased glycolytic flux on insulin secretion may be mediated perhaps via changes in the NADH/NAD+ ratio (13). As regards the mechanism of potentiation of insulin release: in the fed state potentiation may be related to an increased glycolytic flux whereas this is not the case during starvation. Here enhancement of cAMP may play a role.
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PMID:The role of phosphoenolpyruvate and lactate production in insulin secretion. 22 40

Adenylate cyclase of E. coli is a membrane-bound enzyme the function of which is to synthesize a cofactor for processes that are important in metabolic transitions. The depletion from the environment of a supply of a preferred carbon source dictates the requirement for initiating the synthesis of a new metabolic system; this synthesis will require cAMP. After the adaptation period, the requirement for a high level of synthesis diminishes, resulting in a diminished requirement for cAMP. A mechanism for regulating the activity of adenylate cyclase accomplishes the variation in the required cellular cAMP concentrations. In the absence of a transportable carbon source, adenylate cyclase activity is activated by cellular regulators; when carbon sources are transported, the cellular activators are dissipated, resulting in inhibition of adenylate cyclase activity. This scheme is summarized in Fig. 6. Sugar transport systems fall into two categories: one in which the energy for the process comes from PEP (the PTS) and one in which the energy comes from the proton electrochemical gradient. Adenylate cyclase communicates with both of these systems by interacting with intermediates on the pathway to energy generation for driving these two transport processes. Adenylate cyclase couples indirectly to a large array of sugar-specific transport systems by interacting with intermediates common to all the processes. The net result of this regulatory mechanism is that, without physically communicating with the extracellular environment by spanning the membrane, adenylate cyclase effectively senses the presence of external sugars that interact with cells that have become competent to transport them.
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PMID:Escherichia coli adenylate cyclase as a sensor of sugar transport function. 626 80

Sugar uptake and cytoplasmic inducer generation as well as cyclic AMP synthesis are regulated by the phosphoenolpyruvate:sugar phosphotransferase system (PTS) in Gram-negative enteric bacteria. In these organisms, the free form of the glucose-specific Enzyme IIA (IIAglc) of the PTS, which can be phosphorylated on a histidyl residue by PEP and the PTS energy coupling proteins, inhibits the activities of non-PTS carbohydrate permeases and catabolic enzymes. By contrast, the phosphorylated form of IIAglc appears to activate adenylate cyclase, the cyclic AMP biosynthetic enzyme. What is known of the molecular details of these regulatory interactions will be summarized, and a novel regulatory mechanism involving the fructose repressor, FruR, which controls the transcription of genes encoding enzymes which catalyze reactions in central pathways of carbon metabolism, will be presented.
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PMID:Regulatory interactions involving the proteins of the phosphotransferase system in enteric bacteria. 843 44

The phosphoenolpyruvate phosphotransferase system (PEP-PTS) and adenylate cyclase (AC) IV (encoded by BB0723 [cyaB]) are well conserved in different species of Borrelia. However, the functional roles of PEP-PTS and AC in the infectious cycle of Borrelia have not been characterized previously. We examined 12 PEP-PTS transporter component mutants by needle inoculation of mice to assess their ability to cause mouse infection. Transposon mutants with mutations in the EIIBC components (ptsG) (BB0645, thought to be involved in glucose-specific transport) were unable to cause infection in mice, while all other tested PEP-PTS mutants retained infectivity. Infectivity was partially restored in an in trans-complemented strain of the ptsG mutant. While the ptsG mutant survived normally in unfed as well as fed ticks, it was unable to cause infection in mice by tick transmission, suggesting that the function of ptsG is essential to establish infection by either needle inoculation or tick transmission. In Gram-negative organisms, the regulatory effects of the PEP-PTS are mediated by adenylate cyclase and cyclic AMP (cAMP) levels. A recombinant protein encoded by B. burgdorferi BB0723 (a putative cyaB homolog) was shown to have adenylate cyclase activity in vitro; however, mutants with mutations in this gene were fully infectious in the tick-mouse infection cycle, indicating that its function is not required in this process. By transcriptome analysis, we demonstrated that the ptsG gene may directly or indirectly modulate gene expression of Borrelia burgdorferi. Overall, the PEP-PTS glucose transporter PtsG appears to play important roles in the pathogenesis of B. burgdorferi that extend beyond its transport functions.
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PMID:Phosphoenolpyruvate Phosphotransferase System Components Modulate Gene Transcription and Virulence of Borrelia burgdorferi. 2671 7