Search results for "CITRIC ACID"
showing 10 items of 111 documents
Revisiting the Warburg effect: historical dogma versus current understanding
2020
Contrary to Warburg's original thesis, accelerated aerobic glycolysis is not a primary, permanent and universal consequence of dysfunctional or impaired mitochondria compensating for poor ATP yield per mole of glucose. Instead, in most tumours the Warburg effect is an essential part of a 'selfish' metabolic reprogramming, which results from the interplay between (normoxic/hypoxic) hypoxia-inducible factor-1 (HIF-1) overexpression, oncogene activation (cMyc, Ras), loss of function of tumour suppressors (mutant p53, mutant phosphatase and tensin homologue (PTEN), microRNAs and sirtuins with suppressor functions), activated (PI3K-Akt-mTORC1, Ras-Raf-MEK-ERK-cMyc, Jak-Stat3) or deactivated (LKB…
Sensory domain contraction in histidine kinase CitA triggers transmembrane signaling in the membrane-bound sensor
2017
Bacteria use membrane-integral sensor histidine kinases (HK) to perceive stimuli and transduce signals from the environment to the cytosol. Information on how the signal is transmitted across the membrane by HKs is still scarce. Combining both liquid- and solid-state NMR, we demonstrate that structural rearrangements in the extracytoplasmic, citrate-sensing Per-Arnt-Sim (PAS) domain of HK CitA are identical for the isolated domain in solution and in a longer construct containing the membrane-embedded HK and lacking only the kinase core. We show that upon citrate binding, the PAS domain contracts, resulting in a shortening of the C-terminal β-strand. We demonstrate that this contraction of t…
CitA (citrate) and DcuS (C4-dicarboxylate) sensor kinases in thermophilic Geobacillus kaustophilus and Geobacillus thermodenitrificans
2015
The thermophilic Geobacillus thermodenitrificans and Geobacillus kaustophilus are able to use citrate or C4-dicarboxylates like fumarate or succinate as the substrates for growth. The genomes of the sequenced Geobacillus strains (nine strains) each encoded a two-component system of the CitA family. The sensor kinase of G. thermodenitrificans (termed CitAGt) was able to replace CitA of Escherichia coli (CitAEc) in a heterologous complementation assay restoring expression of the CitAEc-dependent citC-lacZ reporter gene and anaerobic growth on citrate. Complementation was specific for citrate. The sensor kinase of G. kaustophilus (termed DcuSGk) was able to replace DcuSEc of E. coli. It respon…
Lactate as a Metabolite and a Regulator in the Central Nervous System
2016
More than two hundred years after its discovery, lactate still remains an intriguing molecule. Considered for a long time as a waste product of metabolism and the culprit behind muscular fatigue, it was then recognized as an important fuel for many cells. In particular, in the nervous system, it has been proposed that lactate, released by astrocytes in response to neuronal activation, is taken up by neurons, oxidized to pyruvate and used for synthesizing acetyl-CoA to be used for the tricarboxylic acid cycle. More recently, in addition to this metabolic role, the discovery of a specific receptor prompted a reconsideration of its role, and lactate is now seen as a sort of hormone, even invol…
Review: Effect of Some Components of Milk- and Soy-Based Infant Formulas on Mineral Bioavailability
2001
Infants' high nutritional needs are fulfilled by mother's milk or infant formulas to provide all the necessary nutrients, among them minerals. Minerals uptake depends not only on mineral content but also on their bioavailability which, in turn, is affected by the different components of the infant formulas. An understanding of these effects would help to improve mineral bioavailability. This work reviews the influence of endogenous (proteins and phytates) and added (ascorbic and citric acid) components in infant formulas on the bioavailability of nutritionally important mineral elements (calcium, zinc, iron and copper) and their interactions. Special attention is given to the influence of p…
Arabidopsis Serine Decarboxylase 1 (SDC1) in Phospholipid and Amino Acid Metabolism
2018
Arabidopsis thaliana serine decarboxylase 1 (SDC1) catalyzes conversion of serine to ethanolamine, the first reaction step of phosphatidylcholine and phosphatidylethanolamine biosynthesis. However, an involvement of SDC1 in amino acid metabolism remains elusive despite that serine is the substrate of SDC1. Here, we showed that SDC1 localizes in mitochondria although phosphatidylcholine and phosphatidylethanolamine are known to be produced in the endoplasmic reticulum (ER). Moreover, we found that overexpression of SDC1 decreased levels of amino acid compounds derived from mitochondrial tricarboxylic acid cycle. These results suggest that mitochondria-localized SDC1 plays an important role i…
Functional differences between l- and d-carnitine in metabolic regulation evaluated using a low-carnitine Nile tilapia model.
2019
Abstractl-Carnitine is essential for mitochondrialβ-oxidation and has been used as a lipid-lowering feed additive in humans and farmed animals.d-Carnitine is an optical isomer ofl-carnitine anddl-carnitine has been widely used in animal feeds. However, the functional differences betweenl- andd-carnitine are difficult to study because of the endogenousl-carnitine background. In the present study, we developed a low-carnitine Nile tilapia model by treating fish with a carnitine synthesis inhibitor, and used this model to investigate the functional differences betweenl- andd-carnitine in nutrient metabolism in fish.l- ord-carnitine (0·4 g/kg diet) was fed to the low-carnitine tilapia for 6 wee…
Betaine and Choline Improve Lipid Homeostasis in Obesity by Participation in Mitochondrial Oxidative Demethylation
2018
We investigated the metabolic effects of betaine (Bet) supplementation on CTP:phosphoethanolamine cytidylyltransferase/Pcyt2 heterozygous mice (HET). HET received either no treatment or were allowed access to 1% Bet supplemented water for 8 weeks. As we previously showed with choline (Cho), Bet improved hypertriglyceridemia, and hepatic steatosis in HET. The protection from obesity associated with reduced hepatic steatosis and increased lipid breakdown in adipocytes was attributed to increased energy requirements for metabolism and elimination of supplemented Bet and Cho. 1H-NMR-based profiling revealed metabolic changes caused by Bet and Cho supplementation. Cho increased the citric acid c…
Synchronizing the release rates of salicylate and indomethacin from degradable chitosan hydrogel and its optimization by definitive screening design.
2018
Abstract Three types of ionically crosslinked (with citric acid) chitosan discs were loaded with the highly water- soluble drug, sodium salicylate (SS) and the poorly water-soluble drug, indomethacin (Ind). In separate experiments the hydrated discs were immersed in a de-crosslinking solution comprising of different concentrations of calcium chloride, which induced a controlled erosion of the discs, a process which was optimized to synchronize the release rates of the two drugs over a predetermined period of time. The optimization was accomplished by manipulating six factors: chitosan MW, its amount in the formulation, the concentration of the crosslinker agent, the concentration of the de-…
CitA/CitB Two-Component System Regulating Citrate Fermentation in Escherichia coli and Its Relation to the DcuS/DcuR System In Vivo
2011
ABSTRACT Citrate fermentation by Escherichia coli requires the function of the citrate/succinate antiporter CitT ( citT gene) and of citrate lyase ( citCDEFXG genes). Earlier experiments suggested that the two-component system CitA/CitB, consisting of the membrane-bound sensor kinase CitA and the response regulator CitB, stimulates the expression of the genes in the presence of citrate, similarly to CitA/CitB of Klebsiella pneumoniae . In this study, the expression of a chromosomal citC-lacZ gene fusion was shown to depend on CitA/CitB and citrate. CitA/CitB is related to the DcuS/DcuR two-component system which induces the expression of genes for fumarate respiration in response to C 4 -di…