Potential Role of Plasmalogens in the Modulation of Biomembrane Morphology

Abstract

Plasmalogens are a subclass of cell membrane glycerophospholipids that typically include vinyl- ether bond at the sn-1 position and polyunsaturated fatty acid at the sn-2 position. They are highly abundant in the neuronal, immune, and cardiovascular cell membranes. Despite the abundance of plasmalogens in a plethora of cells, tissues, and organs, the role of plasmalogens remains unclear. Plasmalogens are required for the proper function of integral membrane proteins, lipid rafts, cell signaling, and differentiation. More importantly, plasmalogens play a crucial role in the cell as an endogenous antioxidant that protects the cell membrane components such as phospholipids, unsaturated fatty acids, and lipoproteins from oxidative stress. The incorporation of vinyl-ether linked with alkyl chains in phospholipids alter the physicochemical properties (e.g., the hydrophilicity of the headgroup), packing density, and conformational order of the phospholipids within the biomembranes. Thus, plasmalogens play a significant role in determining the physical and chemical properties of the biomembrane such as its fluidity, thickness, and lateral pressure of the biomembrane. Insights on the important structural and functional properties of plasmalogens may help us to understand the molecular mechanism of membrane transformation, vesicle formation, and vesicular fusion, especially at the synaptic vesicles where plasmalogens are rich and essential for neuronal function. Although many aspects of plasmalogen phospholipid involvement in membrane transformation identified through in vitro experiments and membrane mimic systems, remain to be confirmed in vivo, the compiled data show many intriguing properties of vinyl-ether bonded lipids that may play a significant role in the structural and morphological changes of the biomembranes. In this review, we present the current limited knowledge of the emerging potential role of plasmalogens as a modulator of the biomembrane morphology.

Destruction of polyunsaturated alkyl/acyl and alkenyl/acyl glycerophosphocholine of plasma lipoproteins during incubation with group V and X secretory phospholipase A2s

“…The degradation, signaling, etiology, and pathology of plasmalogens have been recently reviewed (Dorninger et al, 2020). Another recent review (Almsherqi, 2021) emphasizes the potential role of plasmalogens in the modulation of cell membrane morphology and points out that plasmalogens cannot be regarded to function only as internal antioxidants that maintain membrane lipid and protein integrity.…”

Encapsulation of Docosahexaenoic Acid Oil Substantially Improves the Oxylipin Profile of Rat Tissues

“…Some authors showed in mouse cerebral cortex that DHA-enriched diet reduced the n-6 PUFA content in plasmenylethanolamine, the concentration of which tended to decrease in the tissue, whereas a substantial raise in peroxidation products was observed as well ( 57 ). Considering all the data, high concentrations of DHA in eye may explain a lower content of plasmalogens, which are considered as scavenger agents to protect against oxidation ( 58 ). Nevertheless, the discrepancy between control and DHA-enriched diets remains difficult to explain.…”

Plasmalogenic Lipid Analogs as Platelet-Activating Factor Antagonists: A Potential Novel Class of Anti-inflammatory Compounds

“…Of note, pPE is abundant in brain, especially in gray matter and white matter ( Naughton and Trewhella, 1984 ; Lessig and Fuchs, 2009 ), whereas pPC is highly enriched in heart and skeletal muscles ( Lessig and Fuchs, 2009 ; Braverman and Moser, 2012 ). Various biological functions have been proposed for plasmalogens including their protective role against oxidative damage as well as modulatory role in cell membrane structure and dynamics ( Braverman and Moser, 2012 ; Almsherqi, 2021 ). In addition, plasmalogen deficiency has been reported to be associated with multiple diseases categorized as chronic inflammation triggered by oxidative stress ( Pham et al, 2021 ).…”