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Nonenzymatic Reactions above Phospholipid Surfaces of Biological Membranes: Reactivity of Phospholipids and Their Oxidation Derivatives.

Solís-Calero C, Ortega-Castro J, Frau J, Muñoz F - Oxid Med Cell Longev (2015)

Bottom Line: There are some theoretical studies about the mechanisms of reactions related to these processes on phosphatidylethanolamine surfaces, which hypothesize that cell membrane phospholipids surface environment could enhance some reactions through a catalyst effect.Molecular dynamics simulations performed on phospholipid bilayers models, which include modified phospholipids by these reactions and subsequent reactions that conduct to formation of ALEs and AGEs, have revealed changes in the molecular interactions and biophysical properties of these bilayers as consequence of these reactions.Then, more studies are desirable which could correlate the biophysics of modified phospholipids with metabolism in processes such as aging and diseases such as diabetes, atherosclerosis, and Alzheimer's disease.

View Article: PubMed Central - PubMed

Affiliation: Institut d'Investigació en Ciències de la Salut (IUNICS), Departament de Química, Universitat de les Illes Balears, 07122 Palma de Mallorca, Spain ; Instituto de Investigación Sanitaria de Palma, 07010 Palma, Spain.

ABSTRACT
Phospholipids play multiple and essential roles in cells, as components of biological membranes. Although phospholipid bilayers provide the supporting matrix and surface for many enzymatic reactions, their inherent reactivity and possible catalytic role have not been highlighted. As other biomolecules, phospholipids are frequent targets of nonenzymatic modifications by reactive substances including oxidants and glycating agents which conduct to the formation of advanced lipoxidation end products (ALEs) and advanced glycation end products (AGEs). There are some theoretical studies about the mechanisms of reactions related to these processes on phosphatidylethanolamine surfaces, which hypothesize that cell membrane phospholipids surface environment could enhance some reactions through a catalyst effect. On the other hand, the phospholipid bilayers are susceptible to oxidative damage by oxidant agents as reactive oxygen species (ROS). Molecular dynamics simulations performed on phospholipid bilayers models, which include modified phospholipids by these reactions and subsequent reactions that conduct to formation of ALEs and AGEs, have revealed changes in the molecular interactions and biophysical properties of these bilayers as consequence of these reactions. Then, more studies are desirable which could correlate the biophysics of modified phospholipids with metabolism in processes such as aging and diseases such as diabetes, atherosclerosis, and Alzheimer's disease.

No MeSH data available.


Related in: MedlinePlus

Transition state of reaction between PE (blue color) and acetaldehyde (red colour), showing the boundary translation invariance property of PE-surface periodic model. Arrows and green shadows indicate the direction and the protons involved in the transfer, dotted lines represent hydrogen bonds, and R corresponds to PE molecules which contain the amine groups.
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sch2: Transition state of reaction between PE (blue color) and acetaldehyde (red colour), showing the boundary translation invariance property of PE-surface periodic model. Arrows and green shadows indicate the direction and the protons involved in the transfer, dotted lines represent hydrogen bonds, and R corresponds to PE molecules which contain the amine groups.

Mentions: Theoretical chemistry methods provide an atomistic-level description of the molecular systems, in a resolution that cannot be obtained experimentally, but their application in systems as biological membranes, which are enormously complex in terms of both structure and their dynamical properties, demands high computational power. In these cases, it is necessary to generate models of which nature and size depend on the studied property and the used level of calculus. By theoretical analysis, biological membranes properties have been mostly studied employing molecular mechanics-based methods and compared to first-principles computational studies [32–35]. There were only few studies using density functional theory (DFT) methods [36–38] but using cluster models for studying conformational properties generally. Our group at first obtained a mechanism for nonenzymatic reactions on a model of a phospholipid surface at DFT level of theory [19, 20, 22–24] (Table 1). The developed model of PE surface is a periodic model which has in its unit cell two PE molecules according to the studied reaction and a sufficient number of water molecules for forming hydrogen-bond networks (Figure 1). The procedure for obtaining the mechanisms of reactions included calculating transition states and describing energetic and geometric changes along the reaction coordinates, features difficult to describe based on experimental results only. Periodic boundary conditions were fundamental for these calculations, making it possible to model a phospholipids surface, studying its reactivity at the DFT level, and allowing the equivalent transfer of protons between unit cell images due to their boundary translation invariance property (Scheme 2). This methodology has been applied extensively in theoretical modelling of solid-state materials [39, 40] and little to biological molecules [41].


Nonenzymatic Reactions above Phospholipid Surfaces of Biological Membranes: Reactivity of Phospholipids and Their Oxidation Derivatives.

Solís-Calero C, Ortega-Castro J, Frau J, Muñoz F - Oxid Med Cell Longev (2015)

Transition state of reaction between PE (blue color) and acetaldehyde (red colour), showing the boundary translation invariance property of PE-surface periodic model. Arrows and green shadows indicate the direction and the protons involved in the transfer, dotted lines represent hydrogen bonds, and R corresponds to PE molecules which contain the amine groups.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4419266&req=5

sch2: Transition state of reaction between PE (blue color) and acetaldehyde (red colour), showing the boundary translation invariance property of PE-surface periodic model. Arrows and green shadows indicate the direction and the protons involved in the transfer, dotted lines represent hydrogen bonds, and R corresponds to PE molecules which contain the amine groups.
Mentions: Theoretical chemistry methods provide an atomistic-level description of the molecular systems, in a resolution that cannot be obtained experimentally, but their application in systems as biological membranes, which are enormously complex in terms of both structure and their dynamical properties, demands high computational power. In these cases, it is necessary to generate models of which nature and size depend on the studied property and the used level of calculus. By theoretical analysis, biological membranes properties have been mostly studied employing molecular mechanics-based methods and compared to first-principles computational studies [32–35]. There were only few studies using density functional theory (DFT) methods [36–38] but using cluster models for studying conformational properties generally. Our group at first obtained a mechanism for nonenzymatic reactions on a model of a phospholipid surface at DFT level of theory [19, 20, 22–24] (Table 1). The developed model of PE surface is a periodic model which has in its unit cell two PE molecules according to the studied reaction and a sufficient number of water molecules for forming hydrogen-bond networks (Figure 1). The procedure for obtaining the mechanisms of reactions included calculating transition states and describing energetic and geometric changes along the reaction coordinates, features difficult to describe based on experimental results only. Periodic boundary conditions were fundamental for these calculations, making it possible to model a phospholipids surface, studying its reactivity at the DFT level, and allowing the equivalent transfer of protons between unit cell images due to their boundary translation invariance property (Scheme 2). This methodology has been applied extensively in theoretical modelling of solid-state materials [39, 40] and little to biological molecules [41].

Bottom Line: There are some theoretical studies about the mechanisms of reactions related to these processes on phosphatidylethanolamine surfaces, which hypothesize that cell membrane phospholipids surface environment could enhance some reactions through a catalyst effect.Molecular dynamics simulations performed on phospholipid bilayers models, which include modified phospholipids by these reactions and subsequent reactions that conduct to formation of ALEs and AGEs, have revealed changes in the molecular interactions and biophysical properties of these bilayers as consequence of these reactions.Then, more studies are desirable which could correlate the biophysics of modified phospholipids with metabolism in processes such as aging and diseases such as diabetes, atherosclerosis, and Alzheimer's disease.

View Article: PubMed Central - PubMed

Affiliation: Institut d'Investigació en Ciències de la Salut (IUNICS), Departament de Química, Universitat de les Illes Balears, 07122 Palma de Mallorca, Spain ; Instituto de Investigación Sanitaria de Palma, 07010 Palma, Spain.

ABSTRACT
Phospholipids play multiple and essential roles in cells, as components of biological membranes. Although phospholipid bilayers provide the supporting matrix and surface for many enzymatic reactions, their inherent reactivity and possible catalytic role have not been highlighted. As other biomolecules, phospholipids are frequent targets of nonenzymatic modifications by reactive substances including oxidants and glycating agents which conduct to the formation of advanced lipoxidation end products (ALEs) and advanced glycation end products (AGEs). There are some theoretical studies about the mechanisms of reactions related to these processes on phosphatidylethanolamine surfaces, which hypothesize that cell membrane phospholipids surface environment could enhance some reactions through a catalyst effect. On the other hand, the phospholipid bilayers are susceptible to oxidative damage by oxidant agents as reactive oxygen species (ROS). Molecular dynamics simulations performed on phospholipid bilayers models, which include modified phospholipids by these reactions and subsequent reactions that conduct to formation of ALEs and AGEs, have revealed changes in the molecular interactions and biophysical properties of these bilayers as consequence of these reactions. Then, more studies are desirable which could correlate the biophysics of modified phospholipids with metabolism in processes such as aging and diseases such as diabetes, atherosclerosis, and Alzheimer's disease.

No MeSH data available.


Related in: MedlinePlus