-
1.
Plasma Metabolomics Profile of "Insulin Sensitive" Male Hypogonadism after Testosterone Replacement Therapy.
Zolla, L, Ceci, M
International journal of molecular sciences. 2022;(3)
Abstract
Male hypogonadism is a disorder characterized by low levels of testosterone, but patients can either show normal insulin (insulin-sensitive (IS)) or over time they can become insulin-resistant (IR). Since the two groups showed different altered metabolisms, testosterone replacement therapy (TRT) could achieve different results. In this paper, we analyzed plasma from 20 IS patients with low testosterone (<8 nmol/L) and HOMAi < 2.5. The samples, pre- and post-treatment with testosterone for 60 days, were analyzed by UHPLC and mass spectrometry. Glycolysis was significantly upregulated, suggesting an improved glucose utilization. Conversely, the pentose phosphate pathway was reduced, while the Krebs cycle was not used. Branched amino acids and carnosine metabolism were positively influenced, while β-oxidation of fatty acids (FFA) was not activated. Cholesterol, HDL, and lipid metabolism did not show any improvements at 60 days but did so later in the experimental period. Finally, both malate and glycerol shuttle were reduced. As a result, both NADH and ATP were significantly lower. Interestingly, a significant production of lactate was observed, which induced the activation of the Cori cycle between the liver and muscles, which became the main source of energy for these patients without involving alanine. Thus, the treatment must be integrated with chemicals which are not restored in order to reactivate energy production.
-
2.
The role of water coordination in the pH-dependent gating of hAQP10.
Truelsen, SF, Missel, JW, Gotfryd, K, Pedersen, PA, Gourdon, P, Lindorff-Larsen, K, Hélix-Nielsen, C
Biochimica et biophysica acta. Biomembranes. 2022;(1):183809
Abstract
Human aquaporin 10 (hAQP10) is an aquaglyceroporin that assists in maintaining glycerol flux in adipocytes during lipolysis at low pH. Hence, a molecular understanding of the pH-sensitive glycerol conductance may open up for drug development in obesity and metabolically related disorders. Control of hAQP10-mediated glycerol flux has been linked to the cytoplasmic end of the channel, where a unique loop is regulated by the protonation status of histidine 80 (H80). Here, we performed unbiased molecular dynamics simulations of three protonation states of H80 to unravel channel gating. Strikingly, at neutral pH, we identified a water coordination pattern with an inverted orientation of the water molecules in vicinity of the loop. Protonation of H80 results in a more hydrophobic loop conformation, causing loss of water coordination and leaving the pore often dehydrated. Our results indicate that the loss of such water interaction network may be integral for the destabilization of the loop in the closed configuration at low pH. Additionally, a residue unique to hAQP10 (F85) reveals structural importance by flipping into the channel in correlation with loop movements, indicating a loop-stabilizing role in the closed configuration. Taken together, our simulations suggest a unique gating mechanism combining complex interaction networks between water molecules and protein residues at the loop interface. Considering the role of hAQP10 in adipocytes, the detailed molecular insights of pH-regulation presented here will help to understand glycerol pathways in these cells and may assist in drug discovery for better management of human adiposity and obesity.
-
3.
Culture conditions affect Lactobacillus reuteri DSM 17938 ability to perform glycerol bioconversion into 3-hydroxypropionic acid.
Nguyen, TL, Saulou-Bérion, C, Delettre, J, Béal, C
Journal of bioscience and bioengineering. 2021;(5):501-508
Abstract
The platform molecule 3-hydroxypropionic acid (3-HP) can be produced using Lactobacillus reuteri through a two-step bioprocess that involves a growth phase followed by a bioconversion phase. The bioproduction is performed by resting cells that convert glycerol into 3-HP and 1,3-propanediol in fed-batch mode. This work aimed at studying the effect of the growth conditions of L. reuteri DSM 17938 during the first step, on the glycerol bioconversion into 3-HP during the second step. A Plackett and Burman design was carried out to test, in controlled bioreactors, the effect of 11 growth conditions simultaneously, at fixed bioconversion conditions. The supplementation of the growth medium with vitamin B12 and cysteine displayed a negative effect on the 3-HP bioproduction. The addition of glucose, phytone peptone, Tween 80, 1,2-propanediol and betaine in the growth medium, together with a low temperature and an optimal pH of 6.0 during the growth phase increased the bioconversion duration from 56 h to 89 h at a glycerol feeding rate of 0.5 g·h-1. A validating experiment displayed that the 3-HP titer, 3-HP production yield and 3-HP specific production rate were significantly improved by 25 %, 150 % and 61 %, respectively.
-
4.
Investigation on the Antibacterial Activity of Electronic Cigarette Liquids (ECLs): A Proof of Concept Study.
Fuochi, V, Caruso, M, Emma, R, Stivala, A, Polosa, R, Distefano, A, Furneri, PM
Current pharmaceutical biotechnology. 2021;(7):983-994
Abstract
BACKGROUND The key ingredients of e-cigarettes liquid are commonly propane-1,2-diol (also called propylene glycol) and propane-1,2,3-triol (vegetal glycerol) and their antimicrobial effects are already established. The nicotine and flavors which are often present in e-liquids can interfere with the growth of some microorganisms. OBJECTIVE The effect of combining these elements in e-liquids is unknown. The aim of the study was to investigate the possible effects of these liquids on bacterial growth in the presence or absence of nicotine and flavors. METHODS Susceptibilities of pathogenic strains (Klebsiella pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, Escherichia coli, Enterococcus faecalis and Sarcina lutea) were studied by means of a multidisciplinary approach. Cell viability and antioxidant assays were also evaluated. RESULTS All e-liquids investigated showed antibacterial activity against at least one pathogenic strain. Higher activity was correlated to the presence of flavors and nicotine. DISCUSSION In most cases, the value of minimal bactericidal concentration is equal to the value of minimal inhibitory concentration showing that these substances have a bactericidal effect. This effect was observed in concentrations up to 6.25% v/v. Antioxidant activity was also correlated to the presence of flavors. Over time, the viability assay in human epithelial lung A549 cells showed a dose-dependent inhibition of cell growth. CONCLUSION Our results have shown that flavors considerably enhance the antibacterial activity of propane-1,2-diol and propane-1,2,3-triol. This study provides important evidence that should be taken into consideration in further investigative approaches, to clarify the different sensitivity of the various bacterial species to e-liquids, including the respiratory microbiota, to highlight the possible role of flavors and nicotine.
-
5.
Continuous production of monoacylglycerol via glycerolysis of babassu oil by immobilized Burkholderia cepacia lipase in a packed bed reactor.
Vilas Bôas, RN, Lima, R, Silva, MVC, Freitas, L, Aguiar, LG, de Castro, HF
Bioprocess and biosystems engineering. 2021;(10):2205-2215
Abstract
This study investigated the glycerolysis of babassu oil by Burkholderia cepacia lipase immobilized on SiO2-PVA particles in a continuous packed bed reactor. Experiments were conducted in a solvent-free system at 273.15 K either in an inert atmosphere or in the presence of cocoa butter to prevent lipid oxidation. The reactor (15 × 55 mm) was run at a fixed space time of 9.8 h using different molar ratios of babassu oil to glycerol (1:3, 1:6, 1:9, 1:12, and 1:15) to assess the effects of reactant molar ratio on monoacylglycerol productivity and selectivity. Nitrogen atmosphere and cocoa butter were equally effective in inhibiting lipid oxidation, indicating that addition of cocoa butter to glycerolysis reactions may be an interesting cost-reduction strategy. An oil/glycerol molar ratio of 1:9 resulted in the highest productivity (52.3 ± 2.9 mg g-1 h-1) and selectivity (31.5 ± 1.8%). Residence time distribution data were fitted to an axial dispersion model for closed-vessel boundary conditions, giving a mass transfer coefficient (kc) of 3.4229 × 10-6 m s-1. A kinetic model based on elementary steps of the studied reaction was written in Scilab and compared with experimental data, providing standard deviations in the range of 5.5-7.5%.
-
6.
Computing the Structural Dynamics of RVFV L Protein Domain in Aqueous Glycerol Solutions.
Gogovi, GK, Silayi, S, Shehu, A
Biomolecules. 2021;(10)
Abstract
Many biological and biotechnological processes are controlled by protein-protein and protein-solvent interactions. In order to understand, predict, and optimize such processes, it is important to understand how solvents affect protein structure during protein-solvent interactions. In this study, all-atom molecular dynamics are used to investigate the structural dynamics and energetic properties of a C-terminal domain of the Rift Valley Fever Virus L protein solvated in glycerol and aqueous glycerol solutions in different concentrations by molecular weight. The Generalized Amber Force Field is modified by including restrained electrostatic potential atomic charges for the glycerol molecules. The peptide is considered in detail by monitoring properties like the root-mean-squared deviation, root-mean-squared fluctuation, radius of gyration, hydrodynamic radius, end-to-end distance, solvent-accessible surface area, intra-potential energy, and solvent-peptide interaction energies for hundreds of nanoseconds. Secondary structure analysis is also performed to examine the extent of conformational drift for the individual helices and sheets. We predict that the peptide helices and sheets are maintained only when the modeling strategy considers the solvent with lower glycerol concentration. We also find that the solvent-peptide becomes more cohesive with decreasing glycerol concentrations. The density and radial distribution function of glycerol solvent calculated when modeled with the modified atomic charges show a very good agreement with experimental results and other simulations at 298.15K.
-
7.
Development and characterization of biopolymer films based on bocaiuva (Acromonia aculeata) flour.
Oliveira da Silva, A, Cortez-Vega, WR, Prentice, C, Fonseca, GG
International journal of biological macromolecules. 2020;:1157-1168
Abstract
This work aimed to produce films based on bocaiuva flour (Acrocomia aculeata) by the casting method, and to characterise them. All obtained films were visually symmetrical, without ruptures or blistering and visually homogeneous, easy to handle with a yellowish colouration. The addition of glycerol allowed greater flexibility to the films. The tensile strength and the elongation increase as the concentration of flour increased (2.04 g 100 mL-1). The addition of oily phases increases the elongation, indicating that the essential oil incorporated into the films acted as plasticizer because it also allowed a greater permeability to water vapor. Peaks at 2Ɵ between 10.00°, 13.81°, 17.67°, 20.0° and 24.34° were observed in films with 12.56 g of starch per 100 g of pulp, which are characteristic of B-starch, due to the presence of long branched chains of amylopectin, with a peak characteristic of lignocellulosic materials. Reflection was more intense at 2Ɵ between 22° for all treatments. The obtained films presented relevant characteristics for the application as edible coating.
-
8.
[Conjugation to Branched Glycerol Oligomers, a Novel Strategy for Extremely Hydrophobic Agents].
Miyamoto, L, Abe, S, Nemoto, H, Tsuchiya, K
Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan. 2020;(8):1001-1006
-
-
Free full text
-
Abstract
Ascertaining the absorption, distribution, metabolism, and excretion (ADME) profile of drugs is one of the most crucial factors in the process of drug discovery. Since it is important to combine water solubility and cell permeability within the compound to achieve the desired ADME properties, an appropriate balance between lipophilicity and hydrophilicity is required. It is often necessary to facilitate hydrophilicity of very hydrophobic candidates, because quite lipophobic molecules are rarely hit as positive in molecular-targeted or cell-based screenings. For that purpose, it has been popular to conjugate hydrophobic molecules with polyethylene glycol (PEG). However, PEG is a polymer, and PEG-conjugated molecules are not uniform. Besides, the dosage should be much increased compared with the original molecule due to the increase in molecular weight. Therefore we have been developing alternative ways to endow hydrophobic compounds with extra hydrophilicity by conjugating with symmetrically branched glycerol oligomers. This technology is versatile and easily applicable to various hydrophobic compounds. Water-solubility of fenofibrate, one of the most hydrophobic medicines in clinical use, was facilitated by a factor of more than 2000, and its lipid-lowering effect in vivo improved more than ten-fold, by simply conjugating with branched glycerol trimer, for instance. Here we will briefly introduce the basic concepts and our successful experiences of applying branched glycerol oligomers including antitumor agents in terms of water-solubility, pharmacological effects, and pharmacokinetics, and merits and current issues will be discussed in this review.
-
9.
Structural Basis for Glycerol Efflux and Selectivity of Human Aquaporin 7.
de Maré, SW, Venskutonytė, R, Eltschkner, S, de Groot, BL, Lindkvist-Petersson, K
Structure (London, England : 1993). 2020;(2):215-222.e3
Abstract
The aquaglyceroporin 7 (AQP7) facilitates permeation of glycerol through cell membranes and is crucial for lipid metabolism in humans. Glycerol efflux in human adipocytes is controlled by translocation of AQP7 to the plasma membrane upon hormone stimulation. Here we present two X-ray structures of human AQP7 at 1.9 and 2.2 Å resolution. The structures combined with molecular dynamics simulations suggest that AQP7 is a channel selective for glycerol and that glycerol may hamper water permeation through the channel. Moreover, the high resolution of the structures facilitated a detailed analysis of the orientation of glycerol in the pore, disclosing unusual positions of the hydroxyl groups. The data suggest that glycerol is conducted by a partly rotating movement through the channel. These observations provide a framework for understanding the basis of glycerol efflux and selectivity in aquaglyceroporins and pave the way for future design of AQP7 inhibitors.
-
10.
Anaerobic Sequencing Batch Reactors Co-digesting Whey and Glycerin as a Possible Solution for Small and Mid-size Dairy Industries: Environmental Compliance and Methane Production.
de Albuquerque, JN, Paulinetti, AP, Lovato, G, Albanez, R, Ratusznei, SM, Rodrigues, JAD
Applied biochemistry and biotechnology. 2020;(3):979-998
Abstract
A significant part of whey generated in Brazil is from small and mid-size dairy companies. Cheese whey has great potential for methane production through anaerobic biological processes but presents instabilities due to its high biodegradability. To study an alternative for the destination of this residue, the aim of this work was to investigate methane from the co-digestion of whey with glycerin and its environmental compliance at 55 °C in an anaerobic sequencing batch biofilm reactor. The best performance indicators were obtained with an influent composed of 88% cheese whey and 12% glycerin (by volume), fed-batch mode and organic loading rate of 19.3 kgCOD m-3 day-1 at 55 °C. This operational condition allowed us to achieve a methane productivity of 203 molCH4 m-3 day-1, a methane yield close to theoretical value, and to remove 68% of all organic matter in the influent. A kinetic metabolic model was fitted to the experimental data, which indicated methanogenesis with preference for the acetoclastic route. Finally, the energy production (approximately 197 MWh month-1) from an industrial scale reactor and its volume (three reactors of 152 m3) were assessed for a mid-size dairy industry, which could save up to US$ 22,000.00 per month in oil demand.