alkylglycerols

Alkylglycerol monooxygenase (AGMO) is a tetrahydrobiopterin (BH4)-dependent enzyme with major expression in the liver and white adipose tissue that cleaves alkyl ether glycerolipids. The present study describes the disclosure and biological characterization of a candidate compound (Cp6), which inhibits AGMO with an IC50 of 30-100 µM and 5-20-fold preference of AGMO relative to other BH4-dependent enzymes, i.e., phenylalanine-hydroxylase and nitric oxide synthase. The viability and metabolic activity of mouse 3T3-L1 fibroblasts, HepG2 human hepatocytes and mouse RAW264...

Resistance mechanisms occur in almost all clinical bacterial isolates and represent one of the most worrisome health problems worldwide. Bacteria can form biofilms and communicate through quorum sensing (QS), which allow them to develop resistance against conventional antibiotics. Thus, new therapeutic candidates are sought. We focus on alkylglycerols (AKGs) because of their recently discovered quorum sensing inhibition (QSI) ability and antibiofilm potential. Fifteen natural enantiopure AKGs were tested to determine their effect on the biofilm formation of other clinical bacterial isolates, two reference strains and their QSI was determined using Chromobacterium violaceum ATCC 12472...

Vascular disease contributes to neurodegeneration, which is associated with decreased blood pressure in older humans. Plasmalogens, ether phospholipids produced by peroxisomes, are decreased in Alzheimer's disease, Parkinson's disease, and other neurodegenerative disorders. However, the mechanistic links between ether phospholipids, blood pressure, and neurodegeneration are not fully understood. Here, we show that endothelium-derived ether phospholipids affect blood pressure, behavior, and neurodegeneration in mice...

BACKGROUND: Genome editing in mice using either classical approaches like homologous recombination or CRISPR/Cas9 has been reported to harbor off target effects (insertion/deletion, frame shifts or gene segment duplications) that lead to mutations not only in close proximity to the target site but also outside. Only the genomes of few engineered mouse strains have been sequenced. Since the role of the ether-lipid cleaving enzyme alkylglycerol monooxygenase (AGMO) in physiology and pathophysiology remains enigmatic, we created a knockout mouse model for AGMO using EUCOMM stem cells but unforeseen genotyping issues that did not agree with Mendelian distribution and enzyme activity data prompted an in-depth genomic validation of the mouse model...

The gene encoding alkylglycerol monooxygenase (AGMO) was assigned 10 years ago. So far, AGMO is the only known enzyme capable of catalysing the breakdown of alkylglycerols and lyso-alkylglycerophospholipids. With the knowledge of the genetic information, it was possible to relate a potential contribution for mutations in the AGMO locus to human diseases by genome-wide association studies. A possible role for AGMO was implicated by genetic analyses in a variety of human pathologies such as type 2 diabetes, neurodevelopmental disorders, cancer, and immune defence...

The primacy of lipids as essential components of cellular membranes is conserved across taxonomic domains. In addition to this crucial role as a semi-permeable barrier, lipids are also increasingly recognized as important signaling molecules with diverse functional mechanisms ranging from cell surface receptor binding to the intracellular regulation of enzymatic cascades. In this review, we focus on ether lipids, an ancient family of lipids having ether-linked structures that chemically differ from their more prevalent acyl relatives...

INTRODUCTION AND OBJECTIVE: The anticarcinogenic potential of milk fat can be attributed to its antioxidant, anti-inflammatory, immunostimulatory properties as well as the presence of compounds with antimutagenic effects. In view of the high incidence of cancer the aim of this article was to review the literature concerning the biological activity of milk fat components. BRIEF DESCRIPTION OF THE STATE OF KNOWLEDGE: Conjugated linoleic acid (CLA), coenzyme Q10, phospholipids, β-carotene, and vitamins A, D and E play an important role in the pro-oxidant/antioxidant homeostasis...

Pterins are naturally occurring pigments and enzyme cofactors widespread in living organisms. Tetrahydrobiopterin (H4 Bip) is a coenzyme of aromatic amino acid hydroxylases, NO-synthases, and alkylglycerol monooxygenases. This coenzyme is prone to oxidation in the presence of molecular oxygen, a so-called autoxidation. The reactions participating in H4 Bip autoxidation are well known. However, our study is an attempt to evaluate theoretically the feasibility of reactions participating in autoxidation. To do so, we have calculated the Gibbs free energy of elementary reactions between H4 Bip, its derivatives, molecular oxygen, and reactive oxygen species (ROS)...

O-1-Alkylglycerols are ubiquitous constituents in various biological materials but their biological significance is still largely unknown. So far, reports about the striking role of structural features on the interfacial properties of 1-O-alkylglycerol monolayers are quite rare. Therefore, in the present paper 1-O-alkylglycerol monolayers are comprehensively characterized on mesoscopic and molecular scales in the accessible ranges of temperature and surface pressure. Two Bragg peaks found for the condensed monolayer phase of the racemates at all pressures investigated indicate an orthorhombic structure with NN-tilted alkyl chains at lower pressures and NNN-tilted chains at higher pressures...

Gamecock chickens are one of the earliest recorded birds in China, and have accumulated some unique morphological and behavioral signatures such as large body size, muscularity and aggressive behavior, whereby being excellent breeding materials and a good model for studying bird muscular development and behavior. In this study, we sequenced 126 chicken genomes from 19 populations, including four commercial chicken breeds that are commonly farmed in China, 13 nationwide Chinese typical indigenous chicken breeds (including two Chinese gamecock breeds), one red jungle fowl from Guangxi Province of China and three gamecock chickens from Laos...

Glycerol-based ether lipids including ether phospholipids form a specialized branch of lipids that in mammals require peroxisomes for their biosynthesis. They are major components of biological membranes and one particular subgroup, the plasmalogens, is widely regarded as a cellular antioxidant. Their vast potential to influence signal transduction pathways is less well known. Here, we summarize the literature showing associations with essential signaling cascades for a wide variety of ether lipids, including platelet-activating factor, alkylglycerols, ether-linked lysophosphatidic acid and plasmalogen-derived polyunsaturated fatty acids...

Sjögren-Larsson syndrome (SLS) is an inherited metabolic disease characterized by ichthyosis, spasticity, intellectual disability and deficient oxidation and accumulation of of fatty aldehydes and alcohols. We investigated whether excess fatty alcohols in SLS are diverted into biosynthesis of ether glycerolipids (eGLs) by measuring the 1-O-alkylglycerol (AG) backbone of eGLs in stratum corneum, plasma and red blood cells (RBCs). In all tissues, saturated and monounsaturated AGs were detected. In stratum corneum from SLS patients, saturated AGs (C15-C20) were increased 97-fold (range: 86- to 169-fold) compared to controls...

A significant fraction of the glycerophospholipids in the human body is composed of plasmalogens, particularly in the brain, cardiac, and immune cell membranes. A decline in these lipids has been observed in such diseases as Alzheimer's and chronic obstructive pulmonary disease. Plasmalogens contain a characteristic 1- O -alk-1'-enyl ether (vinyl ether) double bond that confers special biophysical, biochemical, and chemical properties to these lipids. However, the genetics of their biosynthesis is not fully understood, since no gene has been identified that encodes plasmanylethanolamine desaturase (E...

A series of novel substituted 1- O -alkylglycerols (AKGs) containing methoxy ( 8 ), gem -difluoro ( 9 ), azide ( 10 ) and hydroxy ( 11 ) group at 12 position in the alkyl chain were synthesized from commercially available ricinoleic acid ( 12 ). The structures of these new synthesized AKGs were established by NMR experiments as well as from the HRMS and elementary analysis data. The antimicrobial activities of the studied AKGs 8 - 11 were evaluated, respectively, and all compounds exhibited antimicrobial activity to different extents alone and also when combined with some commonly used antibiotics (gentamicin, tetracycline, ciprofloxacin and ampicillin)...

This work studies the effect of enzymatic glycerolysis on digestibility and bioaccessibility of ratfish liver oil (RLO) rich in alkylglycerols (AKGs), as well as the capability of the glycerolysis product (GP) to act as lipid-based delivery system (LBDS) for a supercritical rosemary extract. For comparison purposes, digestibility and bioaccessibility of two additional lipid systems i.e. original RLO and RLO with addition of GRAS monoolein (MO) as emulsifier agent (RLO + MO), have been evaluated. We have studied the efficiency of the GP and RLO + MO lipid systems as LBDS by combining them with a supercritical rosemary extract (RE), i...

Alkylglycerols (AKGs) are bioactive natural compounds that vary by alkyl chain length and degree of unsaturation, and their absolute configuration is 2 S . Three AKGs ( 5l - 5n ) were synthesised in enantiomerically pure form, and were characterised for the first time together with 12 other known and naturally occurring AKGs ( 5a - 5k , 5o ). Their structures were established using 1 H and 13 C APT NMR with 2D-NMR, ESI-MS or HRESI-MS and optical rotation data, and they were tested for their antibacterial and antibiofilm activities...

Alkylglycerol monooxygenase (AGMO) is the only enzyme known to cleave the O-alkyl bonds of ether lipids (alkylglycerols) which are essential components of cell membranes. A homozygous frameshift variant [p.(Glu324LysfsTer12)] in AGMO has recently been reported in two male siblings with syndromic microcephaly. In this study, we identified rare nonsense, in frame deletion, and missense biallelic variants in AGMO in two unrelated individuals with neurodevelopmental disabilities. We assessed the activity of seven disease associated AGMO variants including the four variants identified in our two affected individuals expressed in human embryonic kidney (HEK293T) cells...

The adaptogenic properties of alkylglycerols (AGs) after 1 month's treatment were investigated in a rat model of acute immobilization stress (AIS). The animals receiving AGs 157 mg/kg showed a body weight (BW) decrease in addition to a more pronounced increase in the adrenal glands index under stress conditions. Also, AGs at this dose prevented AIS-induced catalase inhibition. In addition, antiulcerative AG effects were already detected at a dose of 15 mg/kg. The data indicate that AGs promote adrenal gland activation in AIS...

Bioactive supplements display relevant therapeutic properties when properly applied according to validated molecular effects. Our previous research efforts established the basis to develop a dietary supplement based on a Rosmarinus officinalis supercritical extract. This was enriched in phenolic diterpenes (RE) with proven properties against signaling pathways involved in colon tumorigenesis, and shark liver oil rich in alkylglycerols (AKG) as a bioactive lipid vehicle to improve RE bioavailability and synergize with the potential therapeutic action of the extract...

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