S Jackowski

..Thus, the cellular DG supply did not regulate PtdCho biosynthesis and CCT activity governs the partitioning of DG into either the PL or TG pools, thereby controlling both PtdCho and TG biosynthesis...

..The results indicate that although CCTbeta2 is expressed at very low levels compared to the alpha-isoform, loss of CCTbeta2 expression causes a breakdown in the gonadal response to hormonal stimulation...

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..These data support the concept that the expression and/or activity of PanK is a determining factor in the physiological regulation of the intracellular CoA concentration...

..Phosphoethanolamine is a poor substrate. The LicC protein plays a role in the biosynthesis of the phosphocholine-derivatized cell wall constituents that are critical for cell separation and pathogenesis...

..These data indicate that the 2-acyl-GPE acyltransferase and acyl-ACP synthetase reactions are catalyzed by the same membrane protein that possesses a high affinity binding site for soluble ACP...

..The data also demonstrate for the first time that the 57-residue carboxy-terminal domain in CCTalpha participates in lipid-mediated regulation and is sufficient for maximum activation of enzyme activity...

..Since iPLA(2) overexpression did not accelerate either phospholipid remodeling or phosphatidylcholine synthesis, this enzyme does play a determinant (rate-controlling?) role in either of these cellular processes...

..However, extracts from a TLM-resistant mutant (strain CDM5) contained normal levels of TLM-sensitive synthase I activity, illustrating that there are other mechanisms of TLM resistance...

..These data demonstrate that a second, distinct CCT enzyme is expressed in human tissues and provides another mechanism by which cells regulate phosphatidylcholine production...

..The data demonstrate the existence of separate ethanolamine and choline kinases in mammals and show that ethanolamine kinase can be a rate-controlling step in PtdEtn biosynthesis...

..Thus, pantothenate kinase regulation involves the competitive binding of CoA to the ATP site, which blocks ATP binding at one site and prevents positive cooperative ATP binding to the second site on the dimer...

..These data point to acetoacetyl-ACP synthase as a target for thiolactomycin inhibition of bacterial fatty acid biosynthesis...

..Acetyl-CoA inhibition of aPanK was competitive with respect to ATP. Thus, the eukaryotic PanK has a distinct primary structure and unique regulatory properties that clearly distinguish it from its prokaryotic counterpart...

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..CCTbeta3 is not expressed in embryonic brain tissues, but is a significant transcript in the adult. These data suggest unique roles for the CCT protein isoforms in the differential regulation of PtdCho biosynthesis in specific tissues...

..These data illustrate the key role of feedback regulation of pantothenate kinase in the control of intracellular CoA levels...

..Thus, the pantothenamides are pro-antibiotics that inhibit fatty acid synthesis and bacterial growth because of the covalent modification of ACP...

..Thus, the suppression of the fabA6(Ts) mutation by sfa was attributed to its ability to increase the biosynthesis of unsaturated fatty acids...

..The PanK structure provides the framework for a more detailed understanding of the mechanism of catalysis and feedback regulation of PanK...

..The predicted topological profile of pantothenate permease is similar to that of other membrane carriers that catalyze cation-dependent symport...

..These data indicated that a deficiency in de novo PtdCho synthesis could be complemented by altering the metabolism of serum lipoproteins, an alternative source for cellular phospholipid...

..These results identify the metabolic rearrangements that maintain the CoASH pool which is critical to mitochondrial functions, including gluconeogenesis, fatty acid oxidation, and the tricarboxylic acid and urea cycles...

..The purpose of this review is to integrate previous knowledge with the most recent findings in the genetics, enzymology and regulation of CoA biosynthesis in bacteria, plants and mammals...

..These results provide a structural basis for assigning a specific role for magnesium in the catalytic mechanism of pneumococcal LicC...

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..These catalytic properties are consistent with the proposed role of synthase III in the initiation of fatty acid synthesis...

..These data show that CCTalpha expression is required for early embryonic development, but that a 50% reduction in enzyme activity has little detectable impact on the operation of the CDP-choline metabolic pathway in adult tissues...

..Thus, the inability of stimulated B-cells to produce enough phosphatidylcholine prevents proliferation and class switch recombination but leads to unfolded protein response activation and a hyper-IgM secretion phenotype...

..aureus, which lacks glutathione and relies on the CoA/CoA disulfide reductase redox system for protection from oxidative damage...

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..These data place the Ctpct gene on mouse chromosome 16 between the Smst and Stf-1 genes...

..Our results suggest that PanK2 is located in the mitochondria to sense the levels of palmitoylcarnitine and up-regulate CoA biosynthesis in response to an increased mitochondrial demand for the cofactor to support beta-oxidation...

..This work defines a genetic and biochemical program for membrane phospholipid biogenesis that correlates with an increase in the phospholipid components of the endoplasmic reticulum and Golgi compartments in LPS-stimulated B-cells...

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..coli enzyme showed greater selectivity. The overall activity data from these analogues suggest a complex and non-enzyme specific SAR for pantothenamide substrate/inhibitors of the different PanK enzymes...

..Differential expression of the PanK1 alpha and PanK1 beta transcripts would alter the amount of CoA produced in cells as a function of the ratio of free CoA to acetyl-CoA, a reflection of the metabolic status of the tissue...

..These data illustrate that missense mutations that introduce valine at position 390 confer TLM resistance while maintaining the vital catalytic properties of FabB...

..These data identify a novel protein that is phosphorylated in response to mitogenic growth factor stimulation...

..Differences in expression and subcellular localization should be considered in developing a mouse model for human PanK2 deficiency...

..The findings also suggest that PanK1 may be a suitable target for therapeutic intervention in metabolic disorders that feature hyperglycemia and hypertriglyceridemia...

..The absence of the ECT pathway for diacylglycerol utilization at the endoplasmic reticulum triggers increased fatty acid synthesis to support the formation of triacylglycerols leading to liver steatosis...

..These results illustrate a non-redundant role for EtnK2 expression in regulating placental hemostasis...

..We conclude that bacterial inhibition of PtdCho biosynthesis activates an apoptotic cascade that is a causative event in pathogenesis and amenable to therapeutic intervention...

..Our analyses also suggest that the type III PanK in the spore-forming B. anthracis plays an essential role in the novel thiol/disulfide redox biology of this category A biodefense pathogen...

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..We propose that XBP-1(S) regulates ER abundance by coordinately increasing the supply of membrane phospholipids and ER proteins, the key ingredients for ER biogenesis...

..These data suggest that XBP1(S) links the mammalian UPR to phospholipid biosynthesis and ER biogenesis...

..Taken together, our results suggest CCT as a primary target for C(2)-ceramide inhibition that accounts for its cytotoxic effects...

..The research requires expertise in the areas of CoA biosynthesis, lipid metabolism and protein biochemistry which are the clear strengths of the investigative team assembled to pursue this problem. ..

..This research will contribute to the understanding of global metabolic control and human disease by defining the importance of CoA regulation by specific PanK isozymes. ..

..The functions of the CCT regulatory domains characterized in vitro will also be evaluated for cellular localization and membrane binding in living cells. ..

..The research requires expertise in the areas of CoA biosynthesis, lipid metabolism and protein biochemistry which are the clear strengths of the investigative team assembled to pursue this problem. ..

..The research requires expertise in the areas of CoA biosynthesis, lipid metabolism and protein biochemistry which are the clear strengths of the investigative team assembled to pursue this problem. ..

..This research will advance our understanding of the factors that influence cell membrane synthesis and trafficking and then mechanisms that control phospholipid homeostasis in growing cells. ..

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