-
FEBS Letters Sep 2017The biosynthesis of plasmalogens in anaerobic bacteria differs fundamentally from that in animal cells. Firstly, the formation of the alk-1'-enyl ether bond in animal... (Review)
Review
The biosynthesis of plasmalogens in anaerobic bacteria differs fundamentally from that in animal cells. Firstly, the formation of the alk-1'-enyl ether bond in animal cells is oxygen dependent. Secondly, the first step in plasmalogen formation in animal cells is an acylation of dihydroxyacetone phosphate, which has been ruled out as a precursor in anaerobes. In bacteria the alk-1'-enyl ether bond is formed after the fully formed acyl glycerolipids are synthesized. Evidence will be presented for the conversion of the sn-1 acyl-linked chain to an O-alk-1'-enyl ether by an as yet unknown mechanism.
Topics: Acylation; Anaerobiosis; Animals; Clostridium beijerinckii; Dihydroxyacetone Phosphate; Plasmalogens
PubMed: 28617934
DOI: 10.1002/1873-3468.12714 -
Cellular and Molecular Life Sciences :... Jul 1998Reactive oxygen species and alterations in membrane lipid homeostasis are thought to be important events in aging process and aging-related degenerative diseases. The... (Review)
Review
Reactive oxygen species and alterations in membrane lipid homeostasis are thought to be important events in aging process and aging-related degenerative diseases. The peroxisome is a small cellular organelle involved in both oxygen and lipid metabolism, and defects in peroxisomal function are associated with major, and often fatal, changes at the neurological level during human development. Recent reports of aging-related changes in peroxisomal function raised the hypothesis that peroxisomes may also have a significant role in the aging process and aging-related degenerative diseases. This review presents the current data on changes in peroxisomal function during aging and discusses the implications of these changes for health.
Topics: Aging; Antioxidants; Fatty Acids; Lipid Peroxidation; Membrane Lipids; Microbodies; Plasmalogens; Reactive Oxygen Species
PubMed: 9711231
DOI: 10.1007/s000180050192 -
Biochimica Et Biophysica Acta Sep 2012Ether-phospholipids represent an important group of phospholipids characterized by an alkyl or an alkenyl bond at the sn-1 position of the glycerol backbone.... (Review)
Review
Ether-phospholipids represent an important group of phospholipids characterized by an alkyl or an alkenyl bond at the sn-1 position of the glycerol backbone. Plasmalogens are the most abundant form of alkenyl-glycerophospholipids, and their synthesis requires functional peroxisomes. Defects in the biosynthesis of plasmalogens are the biochemical hallmark of the human peroxisomal disorder Rhizomelic Chondrodysplasia Punctata (RCDP), which is characterized by defects in eye, bone and nervous tissue. The generation and characterization of mouse models with defects in plasmalogen levels have significantly advanced our understanding of the role and importance of plasmalogens as well as pathogenetic mechanisms underlying RCDP. A review of the current mouse models and the description of the combined knowledge gathered from the histopathological and biochemical studies is presented and discussed. Further characterization of the role and functions of plasmalogens will contribute to the elucidation of disease pathogenesis in peroxisomal and non-peroxisomal disorders. This article is part of a Special Issue entitled: Metabolic Functions and Biogenesis of Peroxisomes in Health and Disease.
Topics: Animals; Chondrodysplasia Punctata, Rhizomelic; Disease Models, Animal; Glucosamine 6-Phosphate N-Acetyltransferase; Humans; Mice; Mice, Knockout; Peroxisomal Targeting Signal 2 Receptor; Plasmalogens; Receptors, Cytoplasmic and Nuclear
PubMed: 22659211
DOI: 10.1016/j.bbadis.2012.05.014 -
Frontiers in Cell and Developmental... 2022Plasmalogens, functional glycerophospholipids with biological roles in the human body, are associated with various diseases. Although a variety of saturated and/or...
Plasmalogens, functional glycerophospholipids with biological roles in the human body, are associated with various diseases. Although a variety of saturated and/or unsaturated fatty acids in plasmalogens are presumed to have different functions in the human body, there are limited reports validating such functions of plasmalogens. In this study, we focused on the bacterial plasmalogen derived from subsp. (NBRC No. 103574) with different main species of hydrocarbon chains at the -1 position and shorter fatty acids at the -2 position than animal plasmalogens. Optimum culture conditions of for high-yield production of plasmalogens, such as pH and the concentration of caproic acid, were investigated under anaerobic conditions using a 2-L scale jar fermenter. The obtained plasmalogen mainly consisted of the ethanolamine plasmalogen (PlsEtn). The molar ratios of PlsEtn species obtained from , at -1/-2 positions, were p16:1/14:0 (68.4%), p16:1/16:1 (29.2%), p16:1/16:0 (0.7%), p16:1/15:0 (0.3%), and p17:1/14:0 (0.3%). Subsequently, duodenal infusion of the emulsion carrying the lipid extracted from was carried out in lymph duct-cannulated rats. In the lymphatic plasmalogen of rats, the level of PlsEtns with molar ratios p16:1/14:0 and p16:1/16:1, the main species of plasmalogens from , increased gradually until 3-4 h after lipid injection and then gradually decreased. In addition, the level of PlsEtns with p16:1/20:4 and p16:1/22:6 rapidly increased, peaking at 1-1.5 h and 1.5-2 h after lipid injection, respectively. The increase in the number of PlsEtns with p16:1/20:4 and p16:1/22:6 suggested that 20:4 and 22:6, the main fatty acids at the -2 position in the rat lymphatic plasmalogen, were preferentially re-esterified at the -2 position, regardless of the types of hydrocarbon chains at the -1 position. Thus, we showed that bacterial PlsEtns with "unnatural" structures against rats could be absorbed into the lymph. Our findings provide insights into the association between the chemical structure of plasmalogens and their biological functions in humans.
PubMed: 35392167
DOI: 10.3389/fcell.2022.836186 -
Frontiers in Cell and Developmental... 2021Neonatal respiratory distress syndrome (NRDS) is a type of newborn disorder caused by the deficiency or late appearance of lung surfactant, a mixture of lipids and... (Review)
Review
Neonatal respiratory distress syndrome (NRDS) is a type of newborn disorder caused by the deficiency or late appearance of lung surfactant, a mixture of lipids and proteins. Studies have shown that lung surfactant replacement therapy could effectively reduce the morbidity and mortality of NRDS, and the therapeutic effect of animal-derived surfactant preparation, although with its limitations, performs much better than that of protein-free synthetic ones. Plasmalogens are a type of ether phospholipids present in multiple human tissues, including lung and lung surfactant. Plasmalogens are known to promote and stabilize non-lamellar hexagonal phase structure in addition to their significant antioxidant property. Nevertheless, they are nearly ignored and underappreciated in the lung surfactant-related research. This report will focus on plasmalogens, a minor yet potentially vital component of lung surfactant, and also discuss their biophysical properties and functions as anti-oxidation, structural modification, and surface tension reduction at the alveolar surface. At the end, we boldly propose a novel synthetic protein-free lung surfactant preparation with plasmalogen modification as an alternative strategy for surfactant replacement therapy.
PubMed: 33681198
DOI: 10.3389/fcell.2021.618102 -
Journal of Oleo Science Feb 2021Ethanolamine plasmalogen (PlsEtn), a subclass of ethanolamine glycerophospholipid (EtnGpl), has been reported to have many biological and dietary functions. In terms of...
Ethanolamine plasmalogen (PlsEtn), a subclass of ethanolamine glycerophospholipid (EtnGpl), has been reported to have many biological and dietary functions. In terms of PlsEtn absorption, some studies have reported that PlsEtn is re-esterized at the sn-2 position using lymph cannulation and the everted jejunal sac model. In this study, we aimed to better understand the uptake kinetics of PlsEtn and increase its absorption. We thus compared the uptake kinetics of PlsEtn with that of the lyso-form, in which the fatty acid at the sn-2 position was hydrolyzed enzymatically. Upon administration of EtnGpl (extracted from oysters or ascidians, 75.4 mol% and 88.4 mol% of PlsEtn ratio, respectively), the plasma PlsEtn species in mice showed the highest levels at 4 or 8 hours after administration. In the contrast, administration of the EtnGpl hydrolysate, which contained lysoEtnGpl and free fatty acids, markedly increased the plasma levels of PlsEtn species at 2 h after administration. The area under the plasma concentration-time curve (AUC), especially the AUC of PlsEtn species, was higher with hydrolysate administration than that with EtnGpl administration. These results indicate that EtnGpl hydrolysis accelerated the absorption and metabolism of PlsEtn. Consequently, using a different experimental approach from that used in previous studies, we reconfirmed that PlsEtn species were absorbed via hydrolysis at the sn-2 position, suggesting that hydrolysis in advance could increase PlsEtn uptake.
Topics: Administration, Oral; Animals; Intestinal Absorption; Male; Mice, Inbred ICR; Ostreidae; Plasmalogens; Protein Hydrolysates; Mice
PubMed: 33456005
DOI: 10.5650/jos.ess20223 -
Membranes Aug 2023Plasmalogens are a unique family of cellular glycerophospholipids that contain a vinyl-ether bond. The synthesis of plasmalogens is initiated in peroxisomes and... (Review)
Review
Plasmalogens are a unique family of cellular glycerophospholipids that contain a vinyl-ether bond. The synthesis of plasmalogens is initiated in peroxisomes and completed in the endoplasmic reticulum. Plasmalogens are transported to the post-Golgi compartment, including endosomes and plasma membranes, in a manner dependent on ATP, but not vesicular transport. Plasmalogens are preferentially localized in the inner leaflet of the plasma membrane in a manner dependent on P4-type ATPase ATP8B2, that associates with the CDC50 subunit. Plasmalogen biosynthesis is spatiotemporally regulated by a feedback mechanism that senses the amount of plasmalogens in the inner leaflet of the plasma membrane and controls the stability of fatty acyl-CoA reductase 1 (FAR1), the rate-limiting enzyme for plasmalogen biosynthesis. The physiological consequences of such asymmetric localization and homeostasis of plasmalogens are discussed in this review.
PubMed: 37755186
DOI: 10.3390/membranes13090764 -
Analytica Chimica Acta Nov 2021Changes in plasmalogen glycerophosphoethanolamine (PE-P) composition (structure and abundance) are a key indicator of altered lipid metabolism. Differential changes in...
Changes in plasmalogen glycerophosphoethanolamine (PE-P) composition (structure and abundance) are a key indicator of altered lipid metabolism. Differential changes in the levels of PE-P have been reported in different disease states, including neurodegenerative diseases. Of particular interest, traumatic brain injury (TBI) has resulted in altered expression of glycerophospholipid profiles, including PE-P. To date, most analytical assays assessing PE-P have focused on general lipidomic workflows to evaluate the relative, semi-quantitative abundance of PE-P during disease progression. This approach provides a broad evaluation of PE-P, yet often lacks specificity and sensitivity for individual PE-P structures which is a necessity for robust quantitative data. The present study highlights the development of a targeted, quantitative method using a HILIC separation and selective reaction monitoring mass spectrometry for the confident identification and accurate quantitation of PE-P. Our innovative method incorporates both the sn-1 alkyl vinyl ether and sn-2 acyl chain as product ion transitions, for specific and sensitive quantitation of 100 PE-P structures. Our method also uniquely allowed for the unambiguous assignment and quantitation of di-unsaturated sn-1 PE-P structures, which to date have not been conclusively quantified. Application of this assay to a TBI mouse model resulted in distinct temporal profiles for plasma PE-P up to 28 days post injury. Plasma PE-P were significantly increased 24 h after induced TBI, followed by a gradual reduction to sham concentrations by day 28. Overall, we established a structure-specific, quantitative assay for identification and quantitation of a comprehensive set of PE-P structures with demonstrated relevance to brain injury.
Topics: Animals; Lipidomics; Mass Spectrometry; Mice; Phosphatidylethanolamines; Plasmalogens
PubMed: 34756256
DOI: 10.1016/j.aca.2021.339088 -
Biochimica Et Biophysica Acta.... Apr 2023Alkylglycerol monooxygenase (AGMO) and plasmanylethanolamine desaturase (PEDS1) are enzymes involved in ether lipid metabolism. While AGMO degrades plasmanyl lipids by...
Alkylglycerol monooxygenase (AGMO) and plasmanylethanolamine desaturase (PEDS1) are enzymes involved in ether lipid metabolism. While AGMO degrades plasmanyl lipids by oxidative cleavage of the ether bond, PEDS1 exclusively synthesizes a specific subclass of ether lipids, the plasmalogens, by introducing a vinyl ether double bond into plasmanylethanolamine phospholipids. Ether lipids are characterized by an ether linkage at the sn-1 position of the glycerol backbone and they are found in membranes of different cell types. Decreased plasmalogen levels have been associated with neurological diseases like Alzheimer's disease. Agmo-deficient mice do not present an obvious phenotype under unchallenged conditions. In contrast, Peds1 knockout mice display a growth phenotype. To investigate the molecular consequences of Agmo and Peds1 deficiency on the mouse lipidome, five tissues from each mouse model were isolated and subjected to high resolution mass spectrometry allowing the characterization of up to 2013 lipid species from 42 lipid subclasses. Agmo knockout mice moderately accumulated plasmanyl and plasmenyl lipid species. Peds1-deficient mice manifested striking changes characterized by a strong reduction of plasmenyl lipids and a concomitant massive accumulation of plasmanyl lipids resulting in increased total ether lipid levels in the analyzed tissues except for the class of phosphatidylethanolamines where total levels remained remarkably constant also in Peds1 knockout mice. The rate-limiting enzyme in ether lipid metabolism, FAR1, was not upregulated in Peds1-deficient mice, indicating that the selective loss of plasmalogens is not sufficient to activate the feedback mechanism observed in total ether lipid deficiency.
Topics: Animals; Mice; Plasmalogens; Lipid Metabolism; Lipidomics; Ethers; Mice, Knockout
PubMed: 36690320
DOI: 10.1016/j.bbalip.2023.159285 -
Biochimie Jan 2013Ether lipids are an emerging class of lipids which have so far not been investigated and understood in every detail. They have important roles as membrane components of... (Review)
Review
Ether lipids are an emerging class of lipids which have so far not been investigated and understood in every detail. They have important roles as membrane components of e.g. lens, brain and testis, and as mediators such as platelet-activating factor. The metabolic enzymes for biosynthesis and degradation have been investigated to some extent. As most involved enzymes are integral membrane proteins they are tricky to handle in biochemical protocols. The sequence of some ether lipid metabolising enzymes has only recently been reported and other sequences still remain obscure. Defined enzymes without assigned sequence are known as orphan enzymes. One of these enzymes with uncharacterised sequence is plasmanylethanolamine desaturase, a key enzyme for the biosynthesis of one of the most abundant phospholipids in our body, the plasmalogens. This review aims to briefly summarise known functions of ether lipids, give an overview on their metabolism including the most prominent members, platelet-activating factor and the plasmalogens. A special focus is set on the description of orphan enzymes in ether lipid metabolism and on the successful strategies how four previous orphans have recently been assigned a sequence. Only one of these four was characterised by classical protein purification and sequencing, whereas the other three required alternative strategies such as bioinformatic candidate gene selection and recombinant expression or development of an inhibitor and multidimensional metabolic profiling.
Topics: Cell Membrane; Enzymes; Humans; Lipid Metabolism; Lipids; Phospholipid Ethers; Plasmalogens; Platelet Activating Factor
PubMed: 22771767
DOI: 10.1016/j.biochi.2012.06.027