scholarly journals Vitamin Uptake Alteration

2020 ◽  
Author(s):  
Keyword(s):  
Vitamin Uptake

Discovery of Antibacterial Agents Inhibiting the Energy-Coupling Factor (ECF) Transporters by Structure-Based Virtual Screening

2020 ◽  
Author(s):  
Eleonora Diamanti ◽  
Inda Setyawati ◽  
Spyridon Bousis ◽  
leticia mojas ◽  
lotteke Swier ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Antibacterial Agents ◽  
Antimicrobial Agents ◽  
Energy Coupling ◽  
Coupling Factor ◽  
Design Synthesis ◽  
Screening Design ◽  
Starting Point ◽  
Wide Range ◽  
Vitamin Uptake

Here, we report on the virtual screening, design, synthesis and structure–activity relationships (SARs) of the first class of selective, antibacterial agents against the energy-coupling factor (ECF) transporters. The ECF transporters are a family of transmembrane proteins involved in the uptake of vitamins in a wide range of bacteria. Inhibition of the activity of these proteins could reduce the viability of pathogens that depend on vitamin uptake. Because of their central role in the metabolism of bacteria and their absence in humans, ECF transporters are novel potential antimicrobial targets to tackle infection. The hit compound’s metabolic and plasma stability, the potency (20, MIC Streptococcus pneumoniae = 2 µg/mL), the absence of cytotoxicity and a lack of resistance development under the conditions tested here suggest that this scaffold may represent a promising starting point for the development of novel antimicrobial agents with an unprecedented mechanism of action.<br>

scholarly journals Two Essential Arginine Residues in the T Components of Energy-Coupling Factor Transporters

2009 ◽  
Vol 191 (21) ◽  
pp. 6482-6488 ◽  
Author(s):  
Olivia Neubauer ◽  
Anja Alfandega ◽  
Janna Schoknecht ◽  
Ulrich Sternberg ◽  
Anne Pohlmann ◽  
...  
Keyword(s):  
Atpase Activity ◽  
Transmembrane Protein ◽  
Energy Coupling ◽  
Coupling Factor ◽  
Single Mutation ◽  
Modular Assembly ◽  
Double Mutation ◽  
Arginine Residues ◽  
Uptake Activity ◽  
Vitamin Uptake

ABSTRACT Energy-coupling factor (ECF) transporters, a recently discovered class of importers of micronutrients, are composed of a substrate-specific transmembrane component (S component) and a conserved energy-coupling module consisting of a transmembrane protein (T component) and pairs of ABC ATPases (A proteins). Based on utilization of a dedicated (subclass I) or shared (subclass II) energy-coupling module, ECF systems fall into two subclasses. The T components are the least-characterized proteins of ECF importers, and their function is essentially unknown. Using RcBioN and LmEcfT, the T units of the subclass I biotin transporter (RcBioMNY) of a gram-negative bacterium and of the subclass II folate, pantothenate, and riboflavin transporters of a lactic acid bacterium, respectively, we analyzed the role of two strongly conserved short motifs, each containing an arginine residue. Individual replacement of the two Arg residues in RcBioN reduced ATPase activity, an indicator of the transporter function, by two-thirds without affecting the modular assembly of the RcBioMNY complex. A double Arg-to-Glu replacement destroyed the complex and abolished ATPase activity. The corresponding single mutation in motif II of LmEcfT, as well as a double mutation, led to loss of the T unit from the subclass II ECF transporters and inactivated these systems. A single Arg-to-Glu replacement in motif I, however, abolished vitamin uptake activity without affecting assembly of the modules. Our results indicate that the conserved motif I in T components is essential for intramolecular signaling and, in cooperation with motif II, for subunit assembly of modular ECF transporters.

Energy Coupling Factor-Type ABC Transporters for Vitamin Uptake in Prokaryotes

Biochemistry ◽  
2012 ◽  
Vol 51 (22) ◽  
pp. 4390-4396 ◽  
Author(s):  
Guus B. Erkens ◽  
Maria Majsnerowska ◽  
Josy ter Beek ◽  
Dirk Jan Slotboom
Keyword(s):  
Abc Transporters ◽  
Energy Coupling ◽  
Coupling Factor ◽  
Factor Type ◽  
Vitamin Uptake

scholarly journals ADVERSE EFFECTS AND SIDE EFFECTS ON VITAMIN THERAPY: A REVIEW

2017 ◽  
Vol 10 (5) ◽  
pp. 19 ◽  
Author(s):  
Mejo C Korah ◽  
Junaid Rahman Pv ◽  
R Rajeswari ◽  
Ahana Behanan ◽  
Elizabeth Phoeba Paul ◽  
...  
Keyword(s):  
Side Effects ◽  
Adverse Effects ◽  
Health Professionals ◽  
Genetic Factors ◽  
Mortality Rates ◽  
Health Organizations ◽  
Major Health ◽  
Vitamin Therapy ◽  
Vitamin Uptake ◽  
Anti Hiv

Vitamins are essential to our day to day life. Its shortage in our body can cause many disorders, decreased enzyme activities also affects the genetic factors. Vitamins should be supplied through the diet in the required amount. If it is not supplied properly, vitamin tablets will be prescribed. And also vitamin tablets are the co-medication for therapies like anticancer, anti tubercular, anti viral anti HIV treatments. Many news papers reported that vitamin therapies are causing major health problems like nephro/ urolithiasis, it can increases mortality rates in smokers by increasing the risk of lung cancer, it can cause abortion when it is taken during pregnancy. Thus here we reviewed the adverse effects of vitamin therapy from various reported cases, books, instructions provided from various health organizations and also news papers and magazines. It can help health professionals to control and monitor the vitamin therapies and make awareness about the adverse effects and possible side effects of regular vitamin uptake to society.

scholarly journals Vitamin Uptake Studies on Organisms Isolated from Crop Contents of Turkeys with Pendulous Crop

1961 ◽  
Vol 40 (4) ◽  
pp. 900-904 ◽  
Author(s):  
H.O. Wheeler ◽  
B.L. Reid ◽  
T.M. Ferguson ◽  
J.R. Couch
Keyword(s):  
Uptake Studies ◽  
Vitamin Uptake

scholarly journals A Novel Class of Modular Transporters for Vitamins in Prokaryotes

2008 ◽  
Vol 191 (1) ◽  
pp. 42-51 ◽  
Author(s):  
Dmitry A. Rodionov ◽  
Peter Hebbeln ◽  
Aymerick Eudes ◽  
Josy ter Beek ◽  
Irina A. Rodionova ◽  
...  
Keyword(s):  
Abc Transporters ◽  
Transmembrane Protein ◽  
Energy Coupling ◽  
Coupling Factor ◽  
Human Pathogens ◽  
Gram Positive Bacteria ◽  
New Class ◽  
Vitamin Uptake ◽  
Genome Context ◽  
Nucleotide Binding Proteins

ABSTRACT The specific and tightly controlled transport of numerous nutrients and metabolites across cellular membranes is crucial to all forms of life. However, many of the transporter proteins involved have yet to be identified, including the vitamin transporters in various human pathogens, whose growth depends strictly on vitamin uptake. Comparative analysis of the ever-growing collection of microbial genomes coupled with experimental validation enables the discovery of such transporters. Here, we used this approach to discover an abundant class of vitamin transporters in prokaryotes with an unprecedented architecture. These transporters have energy-coupling modules comprised of a conserved transmembrane protein and two nucleotide binding proteins similar to those of ATP binding cassette (ABC) transporters, but unlike ABC transporters, they use small integral membrane proteins to capture specific substrates. We identified 21 families of these substrate capture proteins, each with a different specificity predicted by genome context analyses. Roughly half of the substrate capture proteins (335 cases) have a dedicated energizing module, but in 459 cases distributed among almost 100 gram-positive bacteria, including numerous human pathogens, different and unrelated substrate capture proteins share the same energy-coupling module. The shared use of energy-coupling modules was experimentally confirmed for folate, thiamine, and riboflavin transporters. We propose the name energy-coupling factor transporters for the new class of membrane transporters.

Development of mechanisms for intestinal absorption of vitamin B12 in growing rats

1963 ◽  
Vol 204 (1) ◽  
pp. 101-104 ◽  
Author(s):  
Agna Boass ◽  
T. Hastings Wilson
Keyword(s):  
Intrinsic Factor ◽  
Vitamin B ◽  
Newborn Rats ◽  
Drastic Reduction ◽  
Intestinal Uptake ◽  
Growing Rats ◽  
Stages Of Growth ◽  
Vitamin Uptake ◽  
Newborn Animals ◽  
Stimulation Of

Intestinal uptake of vitamin B12, with and without gastric intrinsic factor (IF), was studied with isolated tissue from rats at various stages of growth. The intestine from fetal and newborn animals showed extremely high uptake of the vitamin in the absence of IF. This IF-independent B12 uptake fell rapidly with time, approaching adult levels at about 14 days. Stimulation of B12 uptake by IF was detectable in the intestine of newborn rats in spite of the high vitamin uptake in its absence. The per cent stimulation due to added IF increased during the 1st 2 weeks because of drastic reduction of the IF-independent B12 uptake. The development of IF and pepsinogen in the stomach of growing rats was also investigated. The stomach wall of fetal and newborn rats contained less than 1% of the IF found in the adult. After the 1st week the amount increased rapidly, reaching adult levels at weaning. A rapid increase in pepsinogen content did not occur until the 3rd week. As the IF-independent transport system decreased in activity, intrinsic factor appeared in the stomach and the adult mechanism became the predominant system for B12 absorption.

scholarly journals Targeting the energy-coupling factor (ECF) transporters: identification of new tool compounds

2021 ◽  
Author(s):  
Eleonora Diamanti ◽  
Inda Setyawati ◽  
Spyridon Bousis ◽  
Paulo C. T. Souza ◽  
leticia mojas ◽  
...  
Keyword(s):  
Energy Coupling ◽  
Coupling Factor ◽  
Coarse Grained ◽  
Design Synthesis ◽  
Screening Design ◽  
Wide Range ◽  
Pharmaceutical Properties ◽  
Vitamin Uptake ◽  
Dynamics Simulations ◽  
Chemical Class

The energy-coupling factor (ECF) transporters are a family of transmembrane proteins involved in the uptake of vitamins in a wide range of bacteria. Inhibition of the activity of these proteins could reduce the viability of pathogens that depend on vitamin uptake. Their central role in the metabolism of bacteria and absence in humans make the ECF transporters a potential antibacterial target, which can be further investigated making use of a selective chemical probe. Here, we report on the virtual screening, design, synthesis, structure–activity relationships (SARs) and coarse-grained molecular dynamics simulations of the first class of inhibitors of the ECF transporters. We investigated the mechanism of action of this chemical class and profiled the best hit compounds regarding their pharmaceutical properties. The optimized hit has a minimum inhibitory concentration (MIC) value of 2 µg/mL against Streptococcus pneumoniae, which opens up the possibility to use this chemical class to investigate the role of the ECF transporters in health and disease.

scholarly journals Identification and targeted management of a neurodegenerative disorder caused by biallelic mutations in SLC5A6

2019 ◽  
Vol 4 (1) ◽  
Author(s):  
Alicia B. Byrne ◽  
Peer Arts ◽  
Steven W. Polyak ◽  
Jinghua Feng ◽  
Andreas W. Schreiber ◽  
...  
Keyword(s):  
Neurodegenerative Disorder ◽  
Genetic Disorder ◽  
Epileptic Encephalopathy ◽  
Compound Heterozygous ◽  
Whole Exome ◽  
Sodium Dependent ◽  
Neuromotor Function ◽  
Vitamin Uptake ◽  
Compound Heterozygous Variants ◽  
Biallelic Mutations

AbstractWe describe a sibling pair displaying an early infantile-onset, progressive neurodegenerative phenotype, with symptoms of developmental delay and epileptic encephalopathy developing from 12 to 14 months of age. Using whole exome sequencing, compound heterozygous variants were identified in SLC5A6, which encodes the sodium-dependent multivitamin transporter (SMVT) protein. SMVT is an important transporter of the B-group vitamins biotin, pantothenate, and lipoate. The protein is ubiquitously expressed and has major roles in vitamin uptake in the digestive system, as well as transport of these vitamins across the blood–brain barrier. Pathogenicity of the identified variants was demonstrated by impaired biotin uptake of mutant SMVT. Identification of this vitamin transporter as the genetic basis of this disorder guided targeted therapeutic intervention, resulting clinically in improvement of the patient’s neurocognitive and neuromotor function. This is the second report of biallelic mutations in SLC5A6 leading to a neurodegenerative disorder due to impaired biotin, pantothenate and lipoate uptake. The genetic and phenotypic overlap of these cases confirms mutations in SLC5A6 as the genetic cause of this disease phenotype. Recognition of the genetic disorder caused by SLC5A6 mutations is essential for early diagnosis and to facilitate timely intervention by triple vitamin (biotin, pantothenate, and lipoate) replacement therapy.

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