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Lutein and Zeaxanthin in the Lipid Bilayer–Similarities and Differences Revealed by Computational Studies

ABSTRACT: Lutein and zeaxanthin are two similar carotenoids of the xanthophyll subgroup. Carotenoids are synthesized almost entirely by plants but are also present in significant amounts in animals. They are essential components of the lipid matrix of biomembranes, and one of their functions is to protect cells from light radiation, free radicals and oxidative stress. Carotenoids, depending on their chemical structure, can locate at various positions and in different orientations in the bilayer. Xanthophylls (XAN) are polar and in the bilayer are positionally restricted. In the case of lutein and zeaxanthin, whose both ionone rings are hydroxy-substituted and as such are anchored in the lipid bilayer interfaces, the position is generally transmembrane. However, both experimental and computer modelling studies indicate that lutein can also locate horizontally below the bilayer interface. This location has never been observed for zeaxanthin. To find a molecular-level explanation for the difference in the orientations of the XAN molecules in the bilayer, a number of phosphatidylcholine-XAN bilayers were constructed and molecular dynamics (MD) simulated for 1.1 µs each. The all-trans XAN molecules were initially placed either parallel or perpendicular to the bilayer surface. With the exception of one lutein, the horizontally placed molecules adopted the transmembrane orientation within 100–600 ns. On the basis of detailed analyses of the XAN orientations and the numbers and lifetimes of their interactions in the bilayer, a plausible explanation is offered as to why a lutein molecule may remain in the horizontal orientation while zeaxanthin does not. Contrary to common believe, lutein horizontal orientation is not related to the ε-ring rotation around the C6′-C7′ bond.

SUBMITTER: Makuch K

PROVIDER: S-EPMC8575744 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:PurposeTo evaluate macular pigment response to carotenoid supplementation in glaucomatous eyes.DesignDouble-masked, randomized, placebo-controlled clinical trial, the European Nutrition in Glaucoma Management Study (ClinicalTrials.gov identifier, NCT04460365).ParticipantsSixty-two participants (38 men, 24 women) with a diagnosis of open-angle glaucoma were enrolled. Forty-two were randomized to receive the active supplement, 20 participants were allocated to placebo.MethodsMacular pigment optical density (MPOD) was measured by autofluorescence using the Heidelberg Spectralis scanning laser ophthalmoscope. Macular pigment optical density volume within the central 6° of retinal eccentricity as well as MPOD at 0.23°, 0.51°, 0.74°, and 1.02° were recorded at baseline and at 6-month intervals over 18 months. Visual function was assessed using visual acuity, mesopic and photopic contrast sensitivity under glare conditions, photo stress recovery time, microperimetry, and Glaucoma Activities Limitation 9 questionnaire. Advanced glaucoma module scans of retinal nerve fiber layer thickness and ganglion cell complex thickness over the central 6° of retinal eccentricity also were completed at each study visit.Main outcome measuresChange in MPOD after supplementation with 10 mg lutein, 2 mg zeaxanthin, and 10 mg meso-zeaxanthin or placebo over 18 months.ResultsA mixed-model repeated measures analysis of variance revealed a statistically significant increase in MPOD volume (significant time effect: F(3,111) = 89.31, mean square error (MSE) = 1656.9; P < 0.01). Post hoc t tests revealed a significant difference in MPOD volume at each study visit for the treatment group (P < 0.01 for all), but no change in the placebo group (P > 0.05 for all). A statistically significant increase in mesopic contrast sensitivity under glare conditions was noted at 18 months in the treatment group, but not placebo. No other structural or functional changes were observed. No serious adverse events were noted during the trial.ConclusionsMacular pigment can be augmented in glaucomatous eyes by supplementation with a formulation containing the carotenoids lutein, zeaxanthin, and meso-zeaxanthin. The greatest relative benefit was observed in those with the lowest baseline levels, but increases were noted across all participants and each retinal eccentricity. The potential benefits of MP augmentation for macular health in glaucoma merit further long-term evaluation.

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Lutein and Zeaxanthin in the Lipid Bilayer–Similarities and Differences Revealed by Computational Studies

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