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Biochimica Et Biophysica Acta.... Jan 2020The turnover of phospholipids plays an essential role in membrane lipid homeostasis by impacting both lipid head group and acyl chain composition. This review focusses... (Review)
Review
The turnover of phospholipids plays an essential role in membrane lipid homeostasis by impacting both lipid head group and acyl chain composition. This review focusses on the degradation and acyl chain remodeling of the major phospholipid classes present in the ER membrane of the reference eukaryote Saccharomyces cerevisiae, i.e. phosphatidylcholine (PC), phosphatidylinositol (PI) and phosphatidylethanolamine (PE). Phospholipid turnover reactions are introduced, and the occurrence and important functions of phospholipid remodeling in higher eukaryotes are briefly summarized. After presenting an inventory of established mechanisms of phospholipid acyl chain exchange, current knowledge of phospholipid degradation and remodeling by phospholipases and acyltransferases localized to the yeast ER is summarized. PC is subject to the PC deacylation-reacylation remodeling pathway (PC-DRP) involving a phospholipase B, the recently identified glycerophosphocholine acyltransferase Gpc1p, and the broad specificity acyltransferase Ale1p. PI is post-synthetically enriched in C18:0 acyl chains by remodeling reactions involving Cst26p. PE may undergo turnover by the phospholipid: diacylglycerol acyltransferase Lro1p as first step in acyl chain remodeling. Clues as to the functions of phospholipid acyl chain remodeling are discussed.
Topics: Acylation; Animals; Endoplasmic Reticulum; Humans; Phosphatidylcholines; Phosphatidylethanolamines; Phosphatidylinositols; Phospholipids; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins
PubMed: 31146038
DOI: 10.1016/j.bbalip.2019.05.006 -
Trends in Plant Science Dec 2017Phospholipids are essential components of biological membranes and signal transduction cascades in plants. In recent years, plant phospholipid research was greatly... (Review)
Review
Phospholipids are essential components of biological membranes and signal transduction cascades in plants. In recent years, plant phospholipid research was greatly advanced by the characterization of numerous mutants affected in phospholipid biosynthesis and the discovery of a number of functionally important phospholipid-binding proteins. It is now accepted that most phospholipids to some extent have regulatory functions, including those that serve as constituents of biological membranes. Phospholipids are more than an inert end product of lipid biosynthesis. This review article summarizes recent advances on phospholipid biosynthesis with a particular focus on polar head group synthesis, followed by a short overview on protein-phospholipid interactions as an emerging regulatory mechanism of phospholipid function in arabidopsis (Arabidopsis thaliana).
Topics: Arabidopsis; Arabidopsis Proteins; Phospholipids
PubMed: 28993119
DOI: 10.1016/j.tplants.2017.09.002 -
Anti-cancer Agents in Medicinal... 2021Cancer is the foremost cause of death, and it supports the need for the identification of novel anticancer drugs to improve the efficacy of current-therapy. While the... (Review)
Review
Cancer is the foremost cause of death, and it supports the need for the identification of novel anticancer drugs to improve the efficacy of current-therapy. While the synthetic anticancer drug is associated with numerous side effects. Hence the plant active or phytoconstituents are in high demand for the treatment of cancer due to minimum side effects. But the polar nature of phytoconstituents hindered the absorption of the drug and lowered the therapeutic efficacy. The plant activity incorporated into Phyto-phospholipid Complexation can enhance bioavailability and improved therapeutic efficacy. In this review article, advantages, limitation and application of Phyto-phospholipid complexes have been illustrated. The article highlights the application of Phyto-phospholipid complexes as a promising drug carrier system to treat cancer.
Topics: Antineoplastic Agents; Biological Availability; Cell Proliferation; Cell Survival; Drug Delivery Systems; Drug Screening Assays, Antitumor; Humans; Molecular Structure; Phospholipids; Phytochemicals
PubMed: 33176666
DOI: 10.2174/1871520620999201110191741 -
Biochimica Et Biophysica Acta Oct 2012The oxidation of lipids has long been a topic of interest in biological and food sciences, and the fundamental principles of non-enzymatic free radical attack on... (Review)
Review
The oxidation of lipids has long been a topic of interest in biological and food sciences, and the fundamental principles of non-enzymatic free radical attack on phospholipids are well established, although questions about detail of the mechanisms remain. The number of end products that are formed following the initiation of phospholipid peroxidation is large, and is continually growing as new structures of oxidized phospholipids are elucidated. Common products are phospholipids with esterified isoprostane-like structures and chain-shortened products containing hydroxy, carbonyl or carboxylic acid groups; the carbonyl-containing compounds are reactive and readily form adducts with proteins and other biomolecules. Phospholipids can also be attacked by reactive nitrogen and chlorine species, further expanding the range of products to nitrated and chlorinated phospholipids. Key to understanding the mechanisms of oxidation is the development of advanced and sensitive technologies that enable structural elucidation. Tandem mass spectrometry has proved invaluable in this respect and is generally the method of choice for structural work. A number of studies have investigated whether individual oxidized phospholipid products occur in vivo, and mass spectrometry techniques have been instrumental in detecting a variety of oxidation products in biological samples such as atherosclerotic plaque material, brain tissue, intestinal tissue and plasma, although relatively few have achieved an absolute quantitative analysis. The levels of oxidized phospholipids in vivo is a critical question, as there is now substantial evidence that many of these compounds are bioactive and could contribute to pathology. The challenges for the future will be to adopt lipidomic approaches to map the profile of oxidized phospholipid formation in different biological conditions, and relate this to their effects in vivo. This article is part of a Special Issue entitled: Oxidized phospholipids-their properties and interactions with proteins.
Topics: Animals; Humans; Lipid Peroxidation; Models, Biological; Organ Specificity; Oxidation-Reduction; Phospholipids
PubMed: 22342938
DOI: 10.1016/j.bbamem.2012.02.002 -
Chemistry and Physics of Lipids Mar 1991To understand the structural bases for the polymorphism of phospholipids, it is often essential to study the properties of "unnatural" phospholipid analogues with... (Review)
Review
To understand the structural bases for the polymorphism of phospholipids, it is often essential to study the properties of "unnatural" phospholipid analogues with modified polar headgroups and or backbone structures. While the thermodynamic characteristics of the "classical" hydrated-gel-to-liquid-crystalline phase transition often appear surprisingly insensitive to these aspects of phospholipid structure, the rich and diverse solid-phase polymorphism of phospholipids is in fact exquisitely sensitive to the nature of both the polar headgroup and the backbone moieties. The tendencies of different phospholipids to form nonlamellar phases at higher temperatures also depend strongly (and in a sometimes surprising manner) on fine details of the headgroup and backbone structures. These points are illustrated by discussions of how the structures of headgroup- and backbone-modified phospholipid analogues influence their proclivities to form distinct types of hydrated solid phases, dehydrated "crystralline" phases and nonlamellar phases.
Topics: Molecular Conformation; Phosphatidylcholines; Phosphatidylethanolamines; Phospholipids; Thermodynamics; Water
PubMed: 2054907
DOI: 10.1016/0009-3084(91)90079-q -
Molecular and Biochemical Parasitology Feb 2003The antiprotozoal activity of phospholipid analogues, originally developed as anti-cancer drugs, has been determined in the past decade. The most susceptible parasites... (Review)
Review
The antiprotozoal activity of phospholipid analogues, originally developed as anti-cancer drugs, has been determined in the past decade. The most susceptible parasites are Leishmania spp. and Trypanosoma cruzi with activity also shown against Trypanosoma brucei spp., Entamoeba histolytica and Acanthamoeba spp. Miltefosine, an alkylphosphocholine, was registered for the oral treatment of visceral leishmaniasis (VL) in India in March 2002. This review will focus on the biological activities of phospholipid analogues. Biochemical and molecular targets and mechanism(s) of action have been studied extensively in tumor cells but have not been determined in protozoa.
Topics: Animals; Antiprotozoal Agents; Leishmania; Parasitic Sensitivity Tests; Phospholipid Ethers; Phospholipids; Phosphorylcholine; Structure-Activity Relationship; Trypanosoma
PubMed: 12615315
DOI: 10.1016/s0166-6851(02)00283-9 -
Progress in Lipid Research 2007Recent advances in electrospray ionisation mass spectrometry (ESI-MS) have greatly facilitated the analysis of phospholipid molecular species in a growing diversity of... (Review)
Review
Recent advances in electrospray ionisation mass spectrometry (ESI-MS) have greatly facilitated the analysis of phospholipid molecular species in a growing diversity of biological and clinical settings. The combination of ESI-MS and metabolic labelling employing substrates labelled with stable isotopes is especially exciting, permitting studies of phospholipid synthesis and turnover in vivo. This review will first describe the methodology involved and will then detail dynamic lipidomic studies that have applied the stable isotope incorporation approach. Finally, it will summarise the increasing number of studies that have used ESI-MS to characterise structural and signalling phospholipid molecular species in development and disease.
Topics: Animals; Cell Differentiation; Cell Membrane; Disease; Health; Humans; Phospholipids; Spectrometry, Mass, Electrospray Ionization
PubMed: 17540449
DOI: 10.1016/j.plipres.2007.04.001 -
Progress in Lipid Research Oct 2013Glycerophospholipids are the most abundant membrane lipid constituents in most eukaryotic cells. As a consequence, phospholipid class and acyl chain homeostasis are... (Review)
Review
Glycerophospholipids are the most abundant membrane lipid constituents in most eukaryotic cells. As a consequence, phospholipid class and acyl chain homeostasis are crucial for maintaining optimal physical properties of membranes that in turn are crucial for membrane function. The topic of this review is our current understanding of membrane phospholipid homeostasis in the reference eukaryote Saccharomyces cerevisiae. After introducing the physical parameters of the membrane that are kept in optimal range, the properties of the major membrane phospholipids and their contributions to membrane structure and dynamics are summarized. Phospholipid metabolism and known mechanisms of regulation are discussed, including potential sensors for monitoring membrane physical properties. Special attention is paid to processes that maintain the phospholipid class specific molecular species profiles, and to the interplay between phospholipid class and acyl chain composition when yeast membrane lipid homeostasis is challenged. Based on the reviewed studies, molecular species selectivity of the lipid metabolic enzymes, and mass action in acyl-CoA metabolism are put forward as important intrinsic contributors to membrane lipid homeostasis.
Topics: Acyl Coenzyme A; Fatty Acids; Membrane Lipids; Phosphatidic Acids; Phospholipids; Saccharomyces cerevisiae
PubMed: 23631861
DOI: 10.1016/j.plipres.2013.04.006 -
Advances in Experimental Medicine and... 1992This article reviews the disposition of intravenously injected phospholipid liposomes and discusses the problems related to its kinetic modeling. The processes... (Review)
Review
This article reviews the disposition of intravenously injected phospholipid liposomes and discusses the problems related to its kinetic modeling. The processes responsible for the plasma clearance of liposomes are examined in detail and it is shown that mechanisms other than reversible distribution to the extravascular space are, as a rule, responsible for the biphasic plasma clearance patterns that are typically observed following bolus intravenous injection of liposomes. Accordingly, a one-compartment open model is generally sufficient to describe the disposition kinetics of phospholipid vesicles. Two factors may be responsible for the observation of a biphasic decline of plasma liposome concentration. The first factor is the presence of different liposomal species with different kinetic behaviors. Kinetically distinct vesicles are present in preparations of liposomes that are heterogeneous in size, since the larger vesicles are cleared at a faster rate than the smaller ones. Different liposomal species may also originate in the plasma as a result of: i) fusion between phospholipid vesicles with generation of larger liposomal structures; and ii) interaction with high-density lipoproteins (HDL) with consequent production of either liposomes that have acquired apoproteins or lipoprotein particles enriched in phospholipids. Both these species are cleared by specific mechanisms at rates different from that of the original vesicle. The second factor is a time-dependent decrease in clearance due to progressive saturation of the retention capacity of the cells that take up liposomes. A convex concentration-time decay curve has also been reported. This decay pattern is consistent with a concentration (dose)-dependent elimination. As this observation relates to only one type of liposome (small unilamellar vesicles composed of sphingomyelin and cholesterol), its relevance to the disposition of liposomes of different size and composition remains to be established.
Topics: Animals; Endocytosis; Injections, Intravenous; Kinetics; Lipoproteins; Liposomes; Membrane Fusion; Phospholipids
PubMed: 1636505
DOI: 10.1007/978-1-4615-3426-6_34 -
Progress in Nucleic Acid Research and... 1998Baker's yeast, Saccharomyces cerevisiae, is an excellent and an increasingly important model for the study of fundamental questions in eukaryotic cell biology and... (Review)
Review
Baker's yeast, Saccharomyces cerevisiae, is an excellent and an increasingly important model for the study of fundamental questions in eukaryotic cell biology and genetic regulation. The fission yeast, Schizosaccharomyces pombe, although not as intensively studied as S. cerevisiae, also has many advantages as a model system. In this review, we discuss progress over the past several decades in biochemical and molecular genetic studies of the regulation of phospholipid metabolism in these two organisms and higher eukaryotes. In S. cerevisiae, following the recent completion of the yeast genome project, a very high percentage of the gene-enzyme relationships in phospholipid metabolism have been assigned and the remaining assignments are expected to be completed rapidly. Complex transcriptional regulation, sensitive to the availability of phospholipid precusors, as well as growth phase, coordinates the expression of the structural genes encoding these enzymes in S. cerevisiae. In this article, this regulation is described, the mechanism by which the cell senses the ongoing metabolic activity in the pathways for phospholipid biosynthesis is discussed, and a model is presented. Recent information relating to the role of phosphatidylcholine turnover in S. cerevisiae and its relationship to the secretory pathway, as well as to the regulation of phospholipid metabolism, is also presented. Similarities in the role of phospholipase D-mediated phosphatidylcholine turnover in the secretory process in yeast and mammals lend further credence to yeast as a model system.
Topics: Phospholipids; Saccharomyces cerevisiae; Schizosaccharomyces
PubMed: 9752720
DOI: 10.1016/s0079-6603(08)60826-0