scholarly journals Immediate inhibition of sucrose uptake inCorynebacterium glutamicumin response to intracellular glucose-6-phosphate accumulation requires theptsGencoded EII-permease

2019 ◽  
Author(s):  
Dimitar P. Petrov ◽  
Oliver Goldbeck ◽  
Reinhard Krämer ◽  
Gerd M. Seibold
Keyword(s):  
Sugar Uptake ◽  
General Strategy ◽  
Good Growth ◽  
Substrate Uptake ◽  
Central Metabolism ◽  
Sucrose Uptake ◽  
Uptake Inhibition ◽  
Glucose Addition ◽  
P Accumulation ◽  
Intracellular Glucose

ABSTRACTCorynebacterium glutamicumco-metabolizes most carbon sources, such as glucose and sucrose. Uptake of those sugars by the PTS involves a glucose- and a sucrose-specific permease EIIGlc(ptsG) and EIISuc(ptsS), respectively. Block of glycolysis by deletion ofpgi(encodes phosphoglucoisomerase) redirects glucose-driven carbon flux towards pentose phosphate pathway.C. glutamicumΔpgigrows poorly with glucose but has unaffected, good growth with sucrose. However, addition of glucose to sucrose-cultivatedC. glutamicumΔpgiimmediately arrested growth via inhibition of the EIISuc–mediated sucrose uptake and reduction ofptsS-mRNA amounts. Kinetic analyses revealed that sucrose uptake inhibition inC. glutamicumΔpgitook place within 15 s after glucose addition. We show that inhibition of PTS-mediated sucrose uptake occurs as direct response to glucose-6-P accumulation. Moreover, addition of non-PTS substrates, which are metabolized to glucose-6-P such as maltose or glucose-6-P itself (uptake was enabled by heterologously produced UhpT), led to similar growth and sucrose uptake inhibition as glucose addition. Despite EIIGlcnot being involved in uptake of these substrates, negative effects on sucrose uptake after addition of maltose and glucose-6-P were absent in the EIIGlc–deficient strainC. glutamicumΔpgiΔptsG. These results show that theptsG-encoded EIIGlcis part of a novel mechanism for perception of intracellular glucose-6-P accumulation and instantaneous inhibition of EIISuc-mediated sucrose uptake inC. glutamicum. This novel mode of control of PTS activity by an early glycolytic metabolite probably allows efficient adaptation of sugar uptake to the capacity of the central metabolism during co-metabolization, which is characteristic forC. glutamicum.IMPORTANCECoordination of substrate uptake and metabolism are a prerequisite for efficient co-utilization of substrates, a trait typical for the Gram-positiveC. glutamicum. Sucrose uptake via the PTS permease EIISucin this organism immediately was inhibited in response to intracellular accumulation of the glycolysis intermediate glucose-6-phosphate. This inhibition depends exclusively on the presence but not activity of the PTS permease EIIGluc. Thus,C. glutamicumpossesses a novel, immediate, and PTS-dependent way to control and coordinate both uptake and metabolization of multiple substrates by monitoring of their metabolic levels in the cell. This offers new insights and interesting concepts for a further rational engineering of this industrially important production organism and exemplifies a putative general strategy of bacteria for the coordination of sugar uptake and central metabolism.

scholarly journals Multiple AMPK activators inhibit l-carnitine uptake in C2C12 skeletal muscle myotubes

2017 ◽  
Vol 312 (6) ◽  
pp. C689-C696 ◽  
Author(s):  
Andy Shaw ◽  
Stewart Jeromson ◽  
Kenneth R. Watterson ◽  
John D. Pediani ◽  
Iain J. Gallagher ◽  
...  
Keyword(s):  
Calcium Release ◽  
Mrna Level ◽  
Calcium Content ◽  
Carnitine Deficiency ◽  
C2c12 Myotubes ◽  
Saturation Curve ◽  
Substrate Uptake ◽  
Uptake Inhibition ◽  
Compound C ◽  
Carnitine Uptake

Mutations in the gene that encodes the principal l-carnitine transporter, OCTN2, can lead to a reduced intracellular l-carnitine pool and the disease Primary Carnitine Deficiency. l-Carnitine supplementation is used therapeutically to increase intracellular l-carnitine. As AMPK and insulin regulate fat metabolism and substrate uptake, we hypothesized that AMPK-activating compounds and insulin would increase l-carnitine uptake in C2C12 myotubes. The cells express all three OCTN transporters at the mRNA level, and immunohistochemistry confirmed expression at the protein level. Contrary to our hypothesis, despite significant activation of PKB and 2DG uptake, insulin did not increase l-carnitine uptake at 100 nM. However, l-carnitine uptake was modestly increased at a dose of 150 nM insulin. A range of AMPK activators that increase intracellular calcium content [caffeine (10 mM, 5 mM, 1 mM, 0.5 mM), A23187 (10 μM)], inhibit mitochondrial function [sodium azide (75 μM), rotenone (1 μM), berberine (100 μM), DNP (500 μM)], or directly activate AMPK [AICAR (250 μM)] were assessed for their ability to regulate l-carnitine uptake. All compounds tested significantly inhibited l-carnitine uptake. Inhibition by caffeine was not dantrolene (10 μM) sensitive despite dantrolene inhibiting caffeine-mediated calcium release. Saturation curve analysis suggested that caffeine did not competitively inhibit l-carnitine transport. To assess the potential role of AMPK in this process, we assessed the ability of the AMPK inhibitor Compound C (10 μM) to rescue the effect of caffeine. Compound C offered a partial rescue of l-carnitine uptake with 0.5 mM caffeine, suggesting that AMPK may play a role in the inhibitory effects of caffeine. However, caffeine likely inhibits l-carnitine uptake by alternative mechanisms independently of calcium release. PKA activation or direct interference with transporter function may play a role.

Towards Systematization

1977 ◽  
Vol 16 (03) ◽  
pp. 125-130 ◽  
Author(s):  
P. L. Reichertz
Keyword(s):  
Clinical Medicine ◽  
Medical Science ◽  
User Involvement ◽  
Empirical Science ◽  
Target System ◽  
General Strategy ◽  
System Construction ◽  
Formal Approach ◽  
Methodology Development ◽  
Planning Development

Data processing has become an important tool in theoretical and clinical medicine. The main categories of applications are : information analysis, (bio)signal processing and the field of information logistics (information systems).The problems encountered lie in the discrepancy of the basic methods of a formal approach to an empirical science, the complexity of the target system and the system ecology, i.e. the involvement of the user and the system environment during system construction and utilization.Possible solutions to these problems are the application of system techniques, inductive planning, development of medical methodology, development of methods and techniques for user involvement and assessment of motivation and education and educational planning.The necessary general strategy in the development in medical informatics is seen in the continuing systematization of the theoretical and practical approach. It is estimated that this will eventually contribute to the systematization of medical science and practice.

Evidence that downregulation of hexose transport limits intracellular glucose in 3T3-L1 fibroblasts

Diabetes ◽  
1990 ◽  
Vol 39 (10) ◽  
pp. 1228-1234 ◽  
Author(s):  
R. R. Whitesell ◽  
D. M. Regen ◽  
D. Pelletier ◽  
N. A. Abumrad
Keyword(s):  
Hexose Transport ◽  
Intracellular Glucose

Tetraphenylbenzene-based AIEgens: the Horizontally Oriented Emitters for highly Efficient Non-doped Deep Blue OLEDs and Host for High-Performance Hybrid WOLEDs

2020 ◽  
Author(s):  
Pengbo Han ◽  
Zeng Xu ◽  
Chengwei Lin ◽  
Dongge Ma ◽  
Anjun Qin ◽  
...  
Keyword(s):  
High Performance ◽  
General Strategy ◽  
Flat Panel Displays ◽  
Light Emitting ◽  
Horizontal Orientation ◽  
Deep Blue ◽  
Full Color ◽  
High Emission ◽  
White Oleds ◽  
Low Efficiency

Deep blue organic-emitting fluorophores are crucial for application in white lighting and full color flat-panel displays but emitters with high color quality and efficiency are rare. Herein, novel deep blue AIE luminogens (AIEgens) with various donor units and an acceptor of cyano substituted tetraphenylbenzene (TPB) cores were developed and used to fabricate non-doped deep blue and hybrid white organic light-emitting diodes (OLEDs). Benefiting from its high emission efficiency and high proportion of horizontally oriented dipoles in the film state, the non-doped deep blue device based on CN-TPB-TPA realized a maximum external quantum efficiency 7.27%, with a low efficiency roll-off and CIE coordinates of (0.15, 0.08). Moreover, efficient two-color hybrid warm white OLEDs (CIE<sub>x,y</sub> = 0.43, 0.45) were achieved using CN-TPB-TPA as the blue-emitting layer and phosphor doped host, which realized maximum current, power, external quantum efficiencies 58.0 cd A<sup>-1</sup>, 60.7 lm W<sup>-1</sup> and 19.1%, respectively. This work provides a general strategy to achieve high performance, stable deep blue and hybrid white OLEDs by construction of AIEgens with excellent horizontal orientation

A One-Pot Chemoenzymatic Synthesis of (2S,4R)-4-Methylproline Enables the First Total Synthesis of Antiviral Lipopeptide Cavinafungin B

2018 ◽  
Author(s):  
Christian R. Zwick ◽  
Hans Renata
Keyword(s):  
Total Synthesis ◽  
Natural Product ◽  
Complex Molecule ◽  
Molecular Target ◽  
Chemoenzymatic Synthesis ◽  
General Strategy ◽  
One Pot

We report an efficient ten-step synthesis of antiviral natural product cavinafungin B in 37% overall yield. By leveraging a one-pot chemoenzymatic synthesis of (2S,4R)-4-methylproline and oxazolidine-tethered (Rink-Boc-ATG-resin) SPPS methodology, the assembly of our molecular target could be conducted in an efficient manner.This general strategy could prove amenable to the construction of other natural and unnatural linear lipopeptides. The value of incorporating biocatalytic steps in complex molecule synthesis is highlighted by this work.

Visible-Light Photosensitized Aryl and Alkyl Decarboxylative Carbon-Heteroatom and Carbon-Carbon Bond Formations

2019 ◽  
Author(s):  
Tuhin Patra ◽  
Satobhisha Mukherjee ◽  
Jiajia Ma ◽  
Felix Strieth-Kalthoff ◽  
Frank Glorius
Keyword(s):  
Energy Transfer ◽  
Visible Light ◽  
Alkyl Radical ◽  
General Strategy ◽  
Alkyl Radicals ◽  
Bond Forming ◽  
Radical Trapping ◽  
Carbon Carbon Bond ◽  
Radical Generation ◽  
Trapping Agent

<sub>A general strategy to access both aryl and alkyl radicals by photosensitized decarboxylation of the corresponding carboxylic acids esters has been developed. An energy transfer mediated homolysis of unsymmetrical sigma-bonds for a concerted fragmentation/decarboxylation process is involved. As a result, an independent aryl/alkyl radical generation step enables a series of key C-X and C-C bond forming reactions by simply changing the radical trapping agent.</sub>

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