China
Africa
Explore chapters and articles related to this topic
Inhibiting Insulin Resistance and Accumulation of Triglycerides and Cholesterol in the Liver
Published in Christophe Wiart, Medicinal Plants in Asia for Metabolic Syndrome, 2017
Ethanol extract of Panax ginseng C. A. Meyer given orally at a dose of 10 g/kg/day to high-fat fed C57BL/6J mice for 13 weeks lowered weight gain from 27.6 to 22.5 g, and body fat from 5.8 to 4.9 g.342 This extract lowered plasma insulin, cholesterol and normalized low-density lipoprotein–cholesterol resulting in a moderation of atherogenic index.342 This treatment downregulated CYP7A1, monoacyl glycerol O-acyltransferase 1, lysosomal lipase, low-density lipoprotein receptor, acyl-CoA thioesterase, and 3-hydroxyl-3-methylglutaryl-coenzyme.342 In hepatocytes, low-density lipoproteins bind to their surface receptors and internalized cholesteryl esters are substrate for lysosomal acid lipase in lysosomes to release fatty acids and free cholesterol.343 Acyl-CoA thioesterase cleave acyl-CoA to produce free fatty acid.344 In the liver, free fatty acids are used for the synthesis of triglycerides, and a key an enzyme of triglyceride synthesis is monoacyl glycerol O-acyltransferase 1, which catalyzes the synthesis of diacyl-glycerol-3-phosphate from fatty acyl-CoA and monoacyl-glycerol-3-phosphate. The expression of this enzyme is increased by peroxisome proliferator-activated receptor-γ and is linked to triglyceride accumulation and steatosis. Wu et al. made the demonstration that in HepG2 cells, increased levels of cyclic adenosine monophosphate activates protein kinase A with subsequent of reduced expression of glycerol-3-phosphate acyltransferase, and decrease in triglyceride contents.345
Bacillus
Published in Dongyou Liu, Laboratory Models for Foodborne Infections, 2017
Jessica Minnaard, Ivanna S. Rolny, Pablo F. Pérez
Cereulide is produced by a non ribosomal peptide synthetase (NRPS) encoded in an operon situated in a virulence plasmid related to the B. anthracis toxin plasmid pXO1.115,116 The gene sequence (ces) that encodes the enzymatic machinery required for the synthesis of cereulide also includes genes encoding a putative hydrolase (cesH), a phosphopantetheinyl transferase (cesP), a type II thioesterase (cesT), and a putative ABC transporter (cesC7D).115,116 Because of its small size and low antigenicity, cereulide is difficult to detect using immunological methods. Instead, assays with cultured cells (Hep-2) allow for the determination of its biological activity leading to vacuole formation and impairment of mitochondrial dehydrogenase activity.109,117–119
Modulation of Lipid Biosynthesis by Stress in Diatoms
Published in Gokare A. Ravishankar, Ranga Rao Ambati, Handbook of Algal Technologies and Phytochemicals, 2019
Bing Huang, Virginie Mimouni, Annick Morant-Manceau, Justine Marchand, Lionel Ulmann, Benoit Schoefs
Thioesterases have also been key targets for lipid bioengineering because they determine the FA chain length. The overexpression of the gene encoding the plastidic thioesterase in P. tricornutum (PtTE) enhanced by two-fold the lipid levels but without modifying the FA composition (Gong et al., 2011). The overexpression of the thioesterase from the land plant Umbellularia californica in P. tricornutum impacted the FA chain length with an increase of 6.2 and 15% in 12:0 and 14:0 respectively. Seventy-five to 90% of these mid-chain FAs were found in TAGs (Radakovits, Eduafo and Posewitz, 2011). Other examples of modifying the FA composition in P. tricornutum involve the targeting of desaturases and elongases that are involved in the synthesis of long chain-polyunsaturated fatty acids (LC-PUFAs) (Dolch and Marechal, 2015). In P. tricornutum, the overexpression of the endogenous Δ5 desaturase, catalyzing the formation of 20:5 from 20:4, conducted to a 65% increase of neutral lipid levels as well as a modification of the FA composition because monounsaturated FA (MUFA) and PUFA levels were increased by 75 and 64%, respectively (Peng et al., 2014). The overexpression of a heterologous Δ5 desaturase from the green picoalga Ostreococcus tauri into P. tricornutum resulted in DHA levels enhanced by eight-fold. DHA was also shown to accumulate in TAG, which exhibited a novel FA composition (Hamilton et al., 2014). Since P. tricornutum naturally produces very low amounts of DHA, this result suggests that this elongation step limits DHA production (Zulu et al., 2018).
In vitro anti-TB properties, in silico target validation, molecular docking and dynamics studies of substituted 1,2,4-oxadiazole analogues against Mycobacterium tuberculosis
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2021
Pran Kishore Deb, Nizar A. Al-Shar’i, Katharigatta N. Venugopala, Melendhran Pillay, Pobitra Borah
In this study, the C-terminal thioesterase (TE) domain of the mycobacterial Polyketide synthase (Pks13) enzyme (Pks13-TE) has been identified as a putative target for the tested compounds. Biologically, the Pks13 enzyme catalyses the last condensation reaction of mycolic acid biosynthesis yielding an oxo‐mycolic acid intermediate which is then reduced to form a mature mycolic acid by a mycolyl reductase97,98,114. Mycolic acids, long α-alkyl-β-hydroxy fatty acids comprising 60–90 carbon atoms, are essential components of the mycobacterial cell wall and are also critical for mycobacterial persistence and pathogenesis115. The majority of mycolic acids are covalently bound to arabinogalactan-peptidoglycan forming the cell wall mycolyl-arabinogalactan-peptidoglycan complex. Moreover, they are associated with outer cell envelope lipids including trehalose monomycolate (TMM), trehalose dimycolate (TDM) and glucose monomycolate, also they can be found as free mycolic acids116,117. Given the prominent role of mycolic acids in mycobacterium cell viability and for virulence, enzymes involved in mycolic acids biosynthesis, such as Pks13, represent novel targets for drug development.
Fatty acid synthase inhibitor orlistat impairs cell growth and down-regulates PD-L1 expression of a human T-cell leukemia line
Published in Journal of Chemotherapy, 2020
Giorgia Cioccoloni, Angelo Aquino, Maria Notarnicola, Maria Gabriella Caruso, Enzo Bonmassar, Manuela Zonfrillo, Simona Caporali, Isabella Faraoni, Cristina Villivà, Maria Pia Fuggetta, Ornella Franzese
Several studies show that orlistat, a tetrahydrolipstatin inhibitor of gastric lipases used for the treatment of obesity, determines the inhibition of FASN, along with suppression of angiogenesis and inhibition of growth in different cancer cell line models.15–18 Interestingly, this compound has also been shown to reduce protein levels of O6-methylguanine-DNA methyltransferase (MGMT), a DNA repair enzyme playing an essential role in the protection against DNA damage provoked by DNA methylating compounds.19 Orlistat generates a covalent adduct with the FASN thioesterase domain,20 thus inhibiting irreversibly the enzymatic activity. This is followed by the activation of apoptotic cascade, mediated by caspase-8, negative regulation of the mTOR pathway21 and cell cycle arrest at the G1/S phase.22 Moreover, FASN is involved in the development of resistance to NK cell cytotoxicity of cisplatin-resistant cancer cells,23 and its inhibition by orlistat increases breast cancer cell susceptibility to anticancer therapies.24
Deciphering metabonomics biomarkers-targets interactions for psoriasis vulgaris by network pharmacology
Published in Annals of Medicine, 2018
Jiangyong Gu, Li Li, Dongmei Wang, Wei Zhu, Ling Han, Ruizhi Zhao, Xiaojie Xu, Chuanjian Lu
Most key enzymes were members of phospholipase A2 family. Various phospholipase A2 types have been implicated in lipid signalling and inflammatory diseases [31]. It has been reported that the activity of phospholipase A2 in human psoriatic skin was regulated by systemic treatment with a retinoic acid derivative [32]. Phospholipase A2 inhibitors have potential therapeutic effects for the treatment of inflammatory diseases [31,33]. Several inhibitors of cytosolic PLA2 are in clinical trials against psoriasis and atopic dermatitis [34]. The human cPLA2 was identified as one of psoriasis-related genes in the psoriatic skin cDNA library [35]. Galectin-10 is expressed in eosinophils and basophils and plays an essential role in immune system by suppression of T cell proliferation [36]. There is no literature that reported the relationship between thioesterase and psoriasis; it might be a new research point.