The Multienzyme Complex Nature of Dehydroepiandrosterone Sulfate Biosynthesis.

Dehydroepiandrosterone (DHEA), a precursor of steroid sex hormones, is synthesized by steroid 17-alpha-hydroxylase/17,20-lyase (CYP17A1) with the participation of microsomal cytochrome b5 (CYB5A) and cytochrome P450 reductase (CPR), followed by sulfation by two cytosolic sulfotransferases, SULT1E1 and SULT2A1, for storage and transport to tissues in which its synthesis is not available. The involvement of CYP17A1 and SULTs in these successive reactions led us to consider the possible interaction of SULTs with DHEA-producing CYP17A1 and its redox partners. Text mining analysis, protein-protein network analysis, and gene co-expression analysis were performed to determine the relationships between SULTs and microsomal CYP isoforms.

In silico design of novel broad anti-HIV-1 agents based on glycosphingolipid β-galactosylceramide, a high-affinity receptor for the envelope gp120 V3 loop.

Novel anti-Human immunodeficiency virus (HIV)-1 agents targeting the V3 loop of envelope protein gp120 were designed by computer modeling based on glycosphingolipid β-galactosylceramide (β-GalCer), which is an alternative receptor allowing HIV-1 entry into CD4-negative cells of neural and colonic origin. Models of these β-GalCer analogs bound to the V3 loops from five various HIV-1 variants were generated by molecular docking and their stability was estimated by molecular dynamics (MDs) and binding free energy simulations. Specific binding to the V3 loop was accomplished primarily by non-conventional XH…π interactions between CH/OH sugar groups of the glycolipids and the conserved V3 residues with π-conjugated side chains.

1-Acyl-2-[N-(2,4-dinitrophenyl)aminopropionyl]-sn-glycero-3-phosphocholine as a chromogenic substrate for phospholipase A₂ assay.

We have developed a spectrophotometric assay for phospholipase A(2) activity using 2,4-dinitrophenyl-labeled phosphatidylcholine as substrate. The assay allows quite simple quantification of phospholipase A(2) activity by measuring the absorbance of the aqueous phase after extraction of the reaction mixture and requires neither chromatographic separation of the reaction products nor the addition of auxiliary coloring reagents.

Formation of phosphatidic acid in stressed mitochondria.

Mitochondria are an important intracellular source of ROS as well as a sensitive target for oxidative damage under certain pathological conditions such as iron or copper overload. Mitochondrial membranes are rich in the tetraacyl phospholipid cardiolipin. Its integrity is important for efficient oxidative phosphorylation.

[The specific diagnostic features of pulmonary tuberculosis at the lower and middle lobular sites].

Cases of pulmonary tuberculosis at the lower and middle lobular are not so rare. However, there is evidence that there is a rise in the number of patients with lower lobular tuberculosis (0.56-15.

[Arachidonoyl amino acids and arachidonoyl peptides: synthesis and properties].

N-Arachidonoyl (AA) derivatives of amino acids (glycine, phenylalanine, proline, valine, gamma-amino butyric acid (GABA), dihydroxyphenylalanine, tyrosine, tryptophan, and alanine) and peptides (Semax, MEHFPGP, and PGP) were synthesized in order to study the biological properties of acylamino acids. The mass spectra of all the compounds at atmospheric pressure electrospray ionization display the most intense peaks of protonated molecular ions; the detection limits for these compounds are 10 fmol per sample. AA-Gly showed the highest inhibitory activity toward fatty acid amide hydrolase from rat brain (IC50 6.

Red/far-red light modulates phospholipase D activity in oat seedlings: relation of enzyme photosensitivity to photosynthesis.

Phospholipase D (PLD) activity was found to be higher in etiolated oat seedlings than in green seedlings. White and red (R) light exposure inhibited PLD activity in etiolated seedlings. Far-red light eliminated R-light-induced decrease in PLD activity, indicating phytochrome participation in observed photomodulation.

Utilizing physiological knowledge to care for acute renal failure.

Nursing can play a pivotal role in promoting positive outcomes in patients who are both at risk of, and experiencing, an episode of acute renal failure (ARF). ARF is potentially recoverable to the extent that 94% of survivors have the potential to be dialysis independent. This article highlights the positive impact ward-based nurses can have on this group of patients through the use of a commonly encountered clinical scenario.

Iron-mediated free-radical formation of signaling lipids in a model system.

It has been shown using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and its combination with thin-layer chromatography (TLC) that the action of the ascorbate/Fe(2+)/H(2)O(2) oxidizing system on cardiolipin and galactocerebroside results in the formation of phosphatidic acid (PA) and ceramide (Cer), respectively. These data, when combined with results obtained on radiolysis of similar substances, allowed the conclusion that the formation of PA and Cer occurs via an OH-induced fragmentation taking place in polar moiety of the starting substrates.

Free-radical fragmentation of galactocerebrosides: a MALDI-TOF mass spectrometry study.

Analysis of final products of radiation-induced transformations of galactocerebrosides (GalCer) in aqueous dispersions has been performed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and its combination of thin-layer chromatography (TLC). Ceramides were found to be the main products of GalCer gamma-radiolysis. From experimental results obtained in this study, as well as from the data available in the literature, an inference is made that the formation of ceramides occurs owing to fragmentation of radicals with an unpaired electron of the C2 atom of the carbohydrate moiety, formed from the starting compounds.

Radiation-induced free-radical transformation of phospholipids: MALDI-TOF MS study.

Under the action of free-radical reaction initiators on membrane phospholipids, complex processes are taking place in both hydrophobic and hydrophilic parts of the phospholipids. Realization of these processes results in a mixture consisting of the initial lipids and their peroxidation and fragmentation products. Identification of compounds in such mixtures requires analytical methods of high sensitivity, reproducibility and accuracy to be applied.

[Bromoacyl analogues of phosphatidylcholine with intramolecular fluorescence quenching and their use as substrates for continuous monitoring of phospholipase A2 activity].

Two new derivatives of phosphatidylcholine with intramolecular fluorescence quenching were obtained by substituting residues of pyrene butyric and bromine-containing fatty acids for acyl chains. The two compounds can be used for quantitative evaluation of catalytic activity of pancreatic phospholipase A2 in kinetic mode.

[Transformation of phospholipids by cabbage phospholipase D in mixed micelles containing 3-[(3-cholamidopropyl)dimethylammonio]propanesulfonate].

We compared the activities of cabbage phospholipase D during hydrolysis and transesterification of phosphatidylcholine in mixed micelles of surface-active compounds with various physicochemical properties. Mixed micelles of phospholipids and 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (ratio, 1:2) were among the best substrates. Hydrolysis and transphosphatidylation were studied in micelles containing 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate.

Novel (3,5-di-tert-butyl-2-hydroxy-phenylcarbamoyl)-alkanoic acids as potent antioxidants.

A series of novel phenolic antioxidants of amphiphilic structure has been synthesized. Investigations into the influence of aliphatic spacer length and nature of a hydrophilic anchor on the antioxidant activity allowed elucidating certain structure requirements for the membrane-addressed antioxidant designing.

Radiation-induced fragmentation of cardiolipin in a model membrane.

Purpose: To obtain evidence for the possibility of free-radical fragmentation of cardiolipin under the action of ionizing radiation as measured by its aqueous dispersion from liposomes.

Materials And Methods: Liposomes of tetramyristoylcardiolipin (TMCL) were exposed to gamma-rays from 60Co or 137Cs sources at doses between 1 and 24kGy. Fragmentation products were identified using thin-layer chromatography and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS).

Formation of phosphatidic acid, ceramide, and diglyceride on radiolysis of lipids: identification by MALDI-TOF mass spectrometry.

By use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, phosphatidic acid was found to be the main product of gamma radiolysis of cardiolipin, phosphatidylinositol, and phosphatidylglycerol. It has been shown that gamma irradiation of such glycolipids as cerebroside and galactosyl diglyceride leads to formation of ceramide and diglyceride, respectively. These findings, combined with those obtained earlier, allowed an assumption to be made that, owing to radiation-induced free radical fragmentation of lipids in their polar moiety, formation of signaling molecules can occur.

[Effect of phosphatidic acid on the radiation-initiated peroxidation of phosphatidylcholine in liposomes].

It was found that the incorporation of anionic dipalmitoyl phosphatidic acid (DPPA) into phosphatidylcholine (PC) liposomes up to 15 mol % was accompanied by the intensification of accumulation of diene conjugates (DC), which are primary products of lipid peroxidation (LPO), if the LPO was initiated by gamma-irradiation of a 137Cs source. Monoethyl ester of DPPA, phosphatidylethanol (DPPEt), exerted a lesser influence at the same concentrations. Ca2+ ions inhibited the DC production not only in liposomes consisting of lipid mixture but in lipid membranes of PC alone as well.

Synthesis and properties of 11-(3,5-di-tert-butyl-2-hydroxyphenylcarbamoyl)undecanoic acid, a new amphiphilic antioxidant.

Based on the membrane addressing concept, designing and synthesis of 11-(3,5-di-tert-butyl-2-hydroxyphenylcarbamoyl)undecanoic acid have been carried out. Antioxidant properties of the prepared compound were investigated in comparison with its non-amphiphilic analogues.

[Effects of complexes of alpha-fetoprotein and amphiphilic docosaenoic acid derivatives on the humoral immune response in C57BL/6 mice].

The immunotropic activity of three derivatives of docosahexaenic acid (N-docosahexaenoyl-L-serine phosphate, N-docosahexaenoyl-L-threonine phosphate, and N-docosahexaenoyl-L-tyrosine phosphate) in complexes with high-purity human alpha-fetoprotein was evaluated. The polyene compounds stimulate the humoral immunity in mice immunized with T-dependent antigen (ram red blood cells). The immunotropic activity of the alpha-fetoprotein-ligand complexes studied depends on the structure and the content of polyene ligands.

Radiation-induced peroxidation and fragmentation of lipids in a model membrane.

Purpose: To ascertain the possibility of fragmentation processes in lipid membranes when acted upon with gamma-radiation under various conditions, and to evaluate fragmentation processes quantitatively in comparison with the lipid peroxidation processes.

Materials And Methods: Phospholipids as components of multilamellar liposomes exposed to 137Cs gamma-rays at dose-rates of 0.06 and 0.

Modification of humoral immune response in C57Bl/6 mice with a complex of alpha-fetoprotein and retinoid acid derivatives.

Amides of all trans-retinoic acid and O-phospho-L-threonine, O-phospho-L-tyrosine, and O-phosphoethanolamine injected intravenously in a dose of 6.8 microg/kg 1.5-3.

Liposomes with phosphatidylethanol as a carrier for oral delivery of insulin: studies in the rat.

In this study, phosphatidylethanol formed by phospholipase D catalysed transphosphatidylation of phosphatidylcholine was employed as a component for preparation of liposomal carrier for oral delivery of insulin. Thermotropic behaviour of liposomes from mixtures of dipalmitoyl phosphatidylcholine and dipalmitoyl phosphatidylethanol, and their resistance to pancreatic phospholipase A(2) catalysed hydrolysis were studied. Three kinds of liposomes with insulin were prepared to examine the pharmacological availability of liposomes with phosphatidylethanol: (i) dipalmitoyl phosphatidylcholine/dipalmitoyl phosphatidylethanol (1:1 w/w) liposomes; (ii) dipalmitoyl phosphatidylcholine/dipalmitoyl phosphatidylethanol/palmitoyl-stearoyl sucrose (1:1:0.

Influence of ethanol and phosphatidylethanol on the activity of pancreatic phospholipase A2.

Hydrolysis of dioleoylphosphatidylethanol (DOPEt) and dioleoylphosphatidylcholine (DOPC) catalyzed by phospholipase A2 (PLA2) from porcine pancreas has been studied in single-component and binary liposomes in the absence and in the presence of ethanol. DOPEt (an anionic phospholipid) was found to increase the rate of hydrolysis of zwitterionic DOPC in liposomes under the action of PLA2.

[Effect of lysophosphatidylcholine on the radiation-induced lipid peroxidation in liposomes].

The effect of lysophosphatidylcholine (LPC) on the lipid peroxidation process (LPO) in liposomes of rat liver phosphatidylcholine initiated by irradiation of 137Cs source was studied. The formation of diene conjugates (DC) is shown to increase dramatically on incorporation of more than 10% LPC into liposomes. The dependence of DC proportion on the irradiation dose is practically linear in the range of 0 to 5 kGy.

[Effect of products of radiation-induced free radical fragmentation of phospholipids and temperature on lipid membranes].

Thermotropic behavior of liposomes exposed to gamma-radiation was studied by differential scanning microcalorimetry. It was found that the peak corresponding to the gel-liquid crystal transition for liposomes composed of bovine brain sphingomyelin and dipalmitoyl phosphatidylglycerol broadened and shifted toward the high-temperature region. No effect of irradiation on dipalmitoyl phosphatidylcholine liposomes was observed.