Competing Interactions of Fatty Acids and Monoglycerides Trigger Synergistic Phospholipid Membrane Remodeling

The phospholipase A2 (PLA2) superfamily contains more than 50 enzymes in mammals that are subdivided into several distinct families on a structural and biochemical basis. In principle, PLA2 has the capacity to hydrolyze the sn-2 position of glycerophospholipids to release fatty acids and lysophospholipids, yet several enzymes in this superfamily catalyze other reactions rather than or in addition to the PLA2 reaction. PLA2 enzymes play crucial roles in not only the production of lipid mediators, but also membrane remodeling, bioenergetics, and body surface barrier, thereby participating in a number of biological events. Accordingly, disturbance of PLA2-regulated lipid metabolism is often associated with various diseases. This review updates the current state of understanding of the classification, enzymatic properties, and biological functions of various enzymes belonging to the PLA2 superfamily, focusing particularly on the novel roles of PLA2s in vivo.

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Examining the Underappreciated Role of S-Acylated Proteins as Critical Regulators of Phagocytosis and Phagosome Maturation in Macrophages

Frontiers in Immunology ◽

10.3389/fimmu.2021.659533 ◽

2021 ◽

Vol 12 ◽

Author(s):

Charneal L. Dixon ◽

Katrina Mekhail ◽

Gregory D. Fairn

Keyword(s):

Signal Transduction ◽

Fatty Acids ◽

Sulfur Atom ◽

Cysteine Residue ◽

Apoptotic Cells ◽

Membrane Remodeling ◽

Phagosome Maturation ◽

Thioester Bond ◽

Acylated Proteins

Phagocytosis is a receptor-mediated process used by cells to engulf a wide variety of particulates, including microorganisms and apoptotic cells. Many of the proteins involved in this highly orchestrated process are post-translationally modified with lipids as a means of regulating signal transduction, membrane remodeling, phagosome maturation and other immunomodulatory functions of phagocytes. S-acylation, generally referred to as S-palmitoylation, is the post-translational attachment of fatty acids to a cysteine residue exposed topologically to the cytosol. This modification is reversible due to the intrinsically labile thioester bond between the lipid and sulfur atom of cysteine, and thus lends itself to a variety of regulatory scenarios. Here we present an overview of a growing number of S-acylated proteins known to regulate phagocytosis and phagosome biology in macrophages.

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Lipid Nanoparticle Technology for Delivering Biologically Active Fatty Acids and Monoglycerides

International Journal of Molecular Sciences ◽

10.3390/ijms22189664 ◽

2021 ◽

Vol 22 (18) ◽

pp. 9664

Author(s):

Jia Ying Brenda Tan ◽

Bo Kyeong Yoon ◽

Nam-Joon Cho ◽

Jasmina Lovrić ◽

Mario Jug ◽

...

Keyword(s):

Fatty Acids ◽

Global Health ◽

Biological Function ◽

Lipid Nanoparticles ◽

Biologically Active ◽

Phospholipid Membrane ◽

Enveloped Viruses ◽

Lipid Nanoparticle ◽

Nanoparticle Structure ◽

Cancer And Inflammation

There is enormous interest in utilizing biologically active fatty acids and monoglycerides to treat phospholipid membrane-related medical diseases, especially with the global health importance of membrane-enveloped viruses and bacteria. However, it is difficult to practically deliver lipophilic fatty acids and monoglycerides for therapeutic applications, which has led to the emergence of lipid nanoparticle platforms that support molecular encapsulation and functional presentation. Herein, we introduce various classes of lipid nanoparticle technology and critically examine the latest progress in utilizing lipid nanoparticles to deliver fatty acids and monoglycerides in order to treat medical diseases related to infectious pathogens, cancer, and inflammation. Particular emphasis is placed on understanding how nanoparticle structure is related to biological function in terms of mechanism, potency, selectivity, and targeting. We also discuss translational opportunities and regulatory needs for utilizing lipid nanoparticles to deliver fatty acids and monoglycerides, including unmet clinical opportunities.

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Lipid constituents of model protocell membranes

Emerging Topics in Life Sciences ◽

10.1042/etls20190021 ◽

2019 ◽

Vol 3 (5) ◽

pp. 537-542 ◽

Cited By ~ 1

Author(s):

Anna Wang ◽

Jack W. Szostak

Keyword(s):

Fatty Acids ◽

Nutrient Transport ◽

Membrane Properties ◽

Membrane Remodeling ◽

Hereditary Material ◽

Cellular Life ◽

Amphiphilic Molecules ◽

Minimal Cells ◽

Insight Into ◽

Highly Evolved

Primitive life must have possessed the essential features of modern cellular life, but without highly evolved proteins to perform dynamic functions such as nutrient transport and membrane remodeling. Here, we consider the membrane properties of protocells — minimal cells with hereditary material, capable of growth and division — and how these properties place restrictions on the components of the membrane. For example, the lipids of modern membranes are diacyl amphiphilic molecules containing well-over 20 carbons in total. Without proteins, these membranes are very stable and kinetically trapped. This inertness, combined with the need for enzymes to synthesize them, makes modern diacyl amphiphiles unsuitable candidates for the earliest membranes on Earth. We, therefore, discuss the progress made thus far with single-chained amphiphiles, including fatty acids and mixtures of fatty acids with related molecules, and the membrane-related research that must be undertaken to gain more insight into the origins of cellular life.

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