A Study on the Possible Occurrence of Base-Exchange Reactions in Vivo

Author(s):  
P. Orlando ◽  
G. Arienti ◽  
P. Saracino ◽  
L. Corazzi ◽  
P. Massari ◽  
...  
1991 ◽  
Vol 273 (1) ◽  
pp. 121-125 ◽  
Author(s):  
G Arthur ◽  
L Page

Studies with mammalian cell lines have led to suggestions that mammalian tissues may derive all of their phosphatidylethanolamine (PE) from the decarboxylation of phosphatidylserine (PS), and also that the physiological significance of the CDP-ethanolamine pathway was the synthesis of ethanolamine plasmalogen. We have therefore investigated the biosynthesis of PE and ethanolamine plasmalogen via the CDP-ethanolamine and decarboxylation pathways in vivo in three rat tissues (heart, kidney and liver), which differ in ethanolamine plasmalogen content. In all three tissues [14C]ethanolamine was incorporated into both PE and ethanolamine plasmalogen, whereas [3H]serine was incorporated into only PS and PE fractions. When [14C]ethanolamine was introduced into the animals, the specific radioactivity of ethanolamine plasmalogen in the kidney was always greater than that of the PE fraction; in the heart the specific radioactivity of the ethanolamine plasmalogen fraction was similar to that of the PE fraction, whereas in the liver the specific radioactivity of the PE fraction was always greater than that of the ethanolamine plasmalogen fraction. The results obtained in this study indicate that: (1) the CDP-ethanolamine pathway is utilized for the synthesis of both PE and ethanolamine plasmalogen in all three tissues; (2) the decarboxylation pathway is utilized solely for the synthesis of PE; (3) serine plasmalogens are not formed by base-exchange reactions; (4) the relative utilization of the CDP-ethanolamine pathway for the synthesis of PE and ethanolamine plasmalogen varies among tissues. Our studies also revealed that the hypolipidaemic drug MDL 29350 is a potent inhibitor of PE N-methyltransferase activity in vitro and in vivo.


2009 ◽  
Vol 29 (4) ◽  
pp. 661-669 ◽  
Author(s):  
Jehoon Yang ◽  
Su Xu ◽  
Jun Shen

In vivo13C magnetic resonance spectroscopy has been applied to studying brain metabolic processes by measuring 13C label incorporation into cytosolic pools such as glutamate and aspartate. However, the rate of exchange between mitochondrial α-ketoglutarate/oxaloacetate and cytosolic glutamate/aspartate ( Vx) extracted from metabolic modeling has been controversial. Because brain fumarase is exclusively located in the mitochondria, and mitochondrial fumarate is connected to cytosolic aspartate through a chain of fast exchange reactions, it is possible to directly measure Vx from the four-carbon side of the tricarboxylic acid cycle by magnetization transfer. In isoflurane-anesthetized adult rat brain, a relayed 13C magnetization transfer effect on cytosolic aspartate C2 at 53.2ppm was detected after extensive signal averaging with fumarate C2 at 136.1ppm irradiated using selective radiofrequency pulses. Quantitative analysis using Bloch–McConnell equations and a four-site exchange model found that VxE13–19 µmol per g per min (≫ VTCA, the tricarboxylic acid cycle rate) when the longitudinal relaxation time of malate C2 was assumed to be within ±33% of that of aspartate C2. If VxE VTCA, the isotopic exchange between mitochondria and cytosol would be too slow on the time scale of 13C longitudinal relaxation to cause a detectable magnetization transfer effect.


1974 ◽  
Vol 52 (6) ◽  
pp. 469-482 ◽  
Author(s):  
M. O. Marshall ◽  
M. Kates

Pathways for biosynthesis of phosphatidylserine (PS), phosphatidylethanolamine (PE), and phosphatidylcholine (PC), in spinach leaves have been studied both in vivo (whole leaves and leaf slices) and in vitro (cell-free leaf fractions). Biosynthesis of PS was shown to occur by the action of a particle-bound CDP-diglyceride: serine phosphatidyltransferase, and PE by the action of a PS-decarboxylase localized in the 100 000 × g supernatant fraction. PE was also formed by the operation of the CDP-ethanolamine:diglyceride phosphorylethanolamine transferase, localized in the microsomal fraction. The presence of ethanolamine kinase required for formation of phosphorylethanolamine was demonstrated in vitro, but not the presence of CTP:phosphorylethanolamine cytidyltransferase; however, the latter is presumed present on the basis of in vivo results. Operation of the methylation pathway for biosynthesis of PC was established in vivo, and direct methylation of phosphatidyl-N-methylethanolamine to phosphatidyl-N,N-dimethylethanolamine (PE-diMe) and of PE-diME to PC by S-adenosylmethionine was demonstrated with a particulate enzyme system localized in the microsomal fraction; direct methylation of PE itself could not be shown in this system. PC was also synthesized by the CDP-choline:diglyceride phosphorylcholine transferase system localized in the microsomal fraction. Synthesis of PE and PC by Ca2+-stimulated exchange reactions with ethanolamine and choline, respectively, could be demonstrated, but at low rates. However, no synthesis of PS by exchange reactions with serine could be detected.


To illustrate the emerging class of anion exchange proteins in bacteria, this article discusses the biochemical and physiological properties of phosphate (Pi)-linked antiporters that accept glucose 6-phosphate (G6P) as their primary substrate. These systems have a bifunctional active site that binds a pair of negative charges, whether presented as a single divalent anion or a pair of monovalent substrates. Exchange stoichiometry therefore .moves between the limits of 2:1 and 2:2 according to the ratio of mono- and divalent substrates at either membrane surface. This predicts an interesting reaction sequence in vivo because internal pH is more alkaline than external pH; one expects an asymmetric exchange as a pair of monovalent G6P anions moves against a single divalent G6P, and in this way an otherwise futile selfexchange of G6P can result in a net inward flux driven (indirectly) by the pH gradient. Despite their biochemical complexity, at a molecular level the Pi-linked antiporters resemble other secondary carriers. Indeed, the current listing of nearly two dozen such proteins suggests a structural theme in which the minimal functional unit has two sets of six transmembrane alpha helices separated by a central hydrophilic loop. Presently described examples show that this topology can derive from either a single protein or from pairs of identical subunits. The finding of this common structure makes it possible to begin building more detailed structural models that have more general implications.


2018 ◽  
Vol 24 (28) ◽  
pp. 3303-3319 ◽  
Author(s):  
Erfaneh Ghassami ◽  
Jaleh Varshosaz ◽  
Somayeh Taymouri

Background: Among the numerous bio-responsive polymeric drug delivery systems developed recently, redox-triggered release of molecular payloads have gained great deal of attention, especially in the field of anticancer drug delivery. In most cases, these systems rely on disulfide bonds located either in the matrix crosslinks, or in auxiliary chains to achieve stimuli-responsive drug release. These bonds keep their stability in extracellular environments, yet, rapidly break by thiol–disulfide exchange reactions in the cytosol, due to the presence of greater levels of glutathione. Polysaccharides are macromolecules with low cost, natural abundance, biocompatibility, biodegradability, appropriate physical and chemical properties, and presence of numerous functional groups which facilitate chemical or physical cross-linking. Methods: With regards to the remarkable advantages of polysaccharides, in the current study, various polysaccharide-based redox-responsive drug delivery systems are reviewed. In most cases the in vitro/in vivo effects of the developed system were also evaluated. Results: Considering the hypoxic and reducing nature of the tumor microenvironment, with several folds higher glutathione levels than the systemic tissues, redox-sensitive polymeric systems could be implemented for tumorspecific drug delivery and the results of the previous researches in this field indicated satisfactory achievements. Conclusion: According to the reviewed papers, the efficiency of diverse redox-responsive polysaccharide-based nanoparticles with therapeutic payloads in cancer chemotherapy could be concluded. Nevertheless, more comprehensive studies are required to understand the exact intracellular and systemic fate of these nano-carriers, as well as their clinical efficacy for cancer treatment.


1994 ◽  
Vol 49 (11-12) ◽  
pp. 781-790 ◽  
Author(s):  
Gerhard Leubner Metzger ◽  
Nikolaus Amrhein

(1-Amino-2-phenylethyl)phosphonic acid (APEP), (1-amino-2-phenylethyl)phosphonous acid (APEPi), α-aminooxy-β-phenylpropionic acid (AOPP) and several other phenylalanine analogues are potent inhibitors of (S)-phenylalanine ammonia-lyase (PAL) in vitro and in vivo. The ability of these compounds to inhibit (S)-phenylalanine-tRNA synthetases (PRSs) from wheat germ, soybean, and baker’s yeast has been investigated and compared to the inhibition of PAL. APEP and APEPi were found to inhibit the tRNAphe-aminoacylation reactions catalyzed by the three PRSs studied in vitro in a competitive manner with respect to (5)-phenylalanine. (R)-APEP inhibits the PRSs with apparent Ki values of 144 μᴍ for wheat germ (app. Km for (S)-phe 5.2 μᴍ) , 130 μᴍ for soybean (app. Km for (S)-phe 0.9 μᴍ) , and 1096 μᴍ for baker’s yeast (app. Km for (S)-phe 5.5 μᴍ ) . The apparent Ki values for (R)-APEPi are 315 μᴍ , 160 μᴍ , and 117 μᴍ , respectively. APEP and APEPi inhibit the ATPpyrophosphate exchange reactions catalyzed by the PRSs from wheat germ and baker’s yeast, but they are not activated and do not serve as substrates in these reactions. AOPP has no affinity to any of the three PRSs, whereas it is a potent inhibitor of PAL. In light of our in vitro results with PRSs from different sources it appears unlikely that the PAL inhibitors we have studied have any significant inhibitory effect on this essential step in protein synthesis in vivo.


2019 ◽  
Vol 9 (8) ◽  
Author(s):  
Saadu Umar Wali ◽  
Kabiru Jega Umar ◽  
Sheikh Danjuma Abubakar ◽  
Ifatokun Paul Ifabiyi ◽  
Ibrahim Mustapha Dankani ◽  
...  

Abstract Groundwater under Basement Complex areas of southern Kebbi has been characterized in order to determine its suitability for drinking and irrigation use. Water samples were drawn from shallow groundwater (hand-dug shallow wells < 5 m) and deep groundwater (boreholes > 40 m). Physical parameters (i.e., temperature, TDS, pH, and EC), were determined in situ, using handheld meters. Discrete water samples were obtained for determination of chemical parameters. Results from several-sample ANOVA (Kruskal–Wallis test) suggested that heterogeneity in water table appeared to exert significant influence on groundwater chemistry which is characterized by a significant difference in pH, EC TH, Na+, Zn2+, Mg2+, PO43−, Cl−, HCO3−, SO42−, and NO3− concentrations. Also, ions including Fe3+, Zn2+, Mg2+, Na+, PO43−, and SO42− are above World Health Organization (2011) and National Standard for Drinking Water Quality (2007) reference guidelines. Most of the groundwater sources are moderately hard. Groundwater classification based on chloride, EC, and TDS revealed water of excellent quality for all types of uses. However, groundwater classification based on nitrate pollution revealed water of poor quality. Rock mineral is the major mechanism controlling water chemistry, as revealed by the Gibbs model. Most of the water sources have positive Scholler index, indicative of overall base exchange reactions in the underlying aquifers. Such condition was well explained by Piper trilinear diagram, which revealed two types of faces: Ca–Mg–HCO3 and Ca–Mg–SO4–Cl. The HCA categorized wells into three groups according to their hydrogeochemical physiognomies. Despite the significant difference in ions concentration and chemical indices, groundwater composition is more influenced by rock weathering than anthropogenic inputs. Groundwater evaluation for irrigation use indicates a significant difference in SAR level which is related to poor permeability index in shallow groundwater. Higher values of Kelly’s index and magnesium adsorption ratio threatened groundwater suitability for irrigation use in the study area.


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