Phosphatidylserine is a phosphoglyceride of fatty acids, attached to a phosphoric ester or phosphoric acid. Phospholipids are the main constituents of animal and plant cell membranes and can be extracted from vegetable fats or eggs. They play an essential role in maintaining the vital organs of the human body, such as the liver and brain.

The name "phosphatidylserine" describes the structure of the molecule:

• "Phosphatidyl-" refers to the phosphatidic acid portion of the molecule.
• "-serine" refers to the amino acid serine, which is attached to the phosphatidic acid.

The synthesis of phosphatidylserine in the body involves a series of enzymatic reactions. Here is a simplified version of the process:

• The process begins with phosphatidylcholine or phosphatidylethanolamine, which are other types of phospholipids.
• An enzyme called phosphatidylserine synthase catalyzes a reaction that replaces the choline or ethanolamine part of the molecule with serine, an amino acid, to form phosphatidylserine.
• The newly formed phosphatidylserine is then incorporated into cell membranes, particularly in the inner leaflet of the lipid bilayer.

What it is for and where

Phosphatidylserine has various applications in medicine:

• Neurology. Phosphatidylserine is highly concentrated in the brain and is involved in maintaining neuronal membrane integrity, synaptic function, and neuroplasticity. It plays a crucial role in supporting cognitive functions such as memory, learning, and attention. Phosphatidylserine supplementation has been studied for its potential benefits in age-related cognitive decline, Alzheimer's disease, and other neurological disorders.
• Stress Reduction. Phosphatidylserine has shown stress-reducing effects by modulating the body's response to stress hormones such as cortisol. It may help mitigate the negative effects of chronic stress and improve mood and psychophysical well-being.
• Attention Deficit Hyperactivity Disorder (ADHD). Phosphatidylserine supplementation has been investigated as a possible adjunct therapy for ADHD. Studies suggest that it may help improve attention, impulsivity, and cognitive performance in individuals with ADHD.
• Sports Performance. Phosphatidylserine supplementation has been studied for its potential benefits in improving sports performance, reducing exercise-induced stress and muscle damage. It may aid in recovery and support optimal muscle function.
• Age-Related Eye Health. Phosphatidylserine has been investigated for its potential role in maintaining healthy vision and supporting eye health, particularly in age-related macular degeneration (AMD) and other retinal conditions.

It is important to note that while phosphatidylserine has shown promising results in these areas, further research is needed to fully understand its mechanisms of action and clinical applications. Before starting phosphatidylserine supplementation for specific medical conditions, it is advisable to consult with a healthcare professional.

Cosmetics

Hair conditioning agent. A significant number of ingredients with specific and targeted purposes may co-exist in hair shampoo formulations: cleansers, conditioners, thickeners, matting agents, sequestering agents, fragrances, preservatives, special additives. However, the indispensable ingredients are the cleansers and conditioners as they are necessary and sufficient for hair cleansing and manageability. The others act as commercial and non-essential auxiliaries such as: appearance, fragrance, colouring, etc. Hair conditioning agents have the task of increasing shine, manageability and volume, and reducing static electricity, especially after treatments such as colouring, ironing, waving, drying and brushing. They are, in practice, dispersants that may contain cationic surfactants, thickeners, emollients, polymers. The typology of hair conditioning agents includes: intensive conditioners, instant conditioners, thickening conditioners, drying conditioners. They can perform their task generally accompanied by other different ingredients.

Skin protectant. It creates a protective barrier on the skin to defend it from harmful substances, irritants, allergens, pathogens that can cause various inflammatory conditions. These products can also improve the natural skin barrier and in most cases more than one is needed to achieve an effective result.

Skin conditioning agent - Miscellaneous.  This ingredient has the task of modifying and improving the condition of the skin when it is damaged or dry, reducing flaking and restoring its elasticity.

• Molecular Formula   C₄₂H₈₂NO₁₀P
• Molecular Weight   792.1 g/mol
• CAS  51446-62-9   1446756-47-3
• UNII    394XK0IH40
• EC Number 
• Nikkaji   J1.757.189C

Compendium of the most significant studies with reference to properties, intake, effects.

Leventis PA, Grinstein S. The distribution and function of phosphatidylserine in cellular membranes. Annu Rev Biophys. 2010;39:407-27. doi: 10.1146/annurev.biophys.093008.131234.

Abstract. Phosphatidylserine (PS) is the most abundant negatively charged phospholipid in eukaryotic membranes. PS directs the binding of proteins that bear C2 or gamma-carboxyglutamic domains and contributes to the electrostatic association of polycationic ligands with cellular membranes. Rather than being evenly distributed, PS is found preferentially in the inner leaflet of the plasma membrane and in endocytic membranes. The loss of PS asymmetry is an early indicator of apoptosis and serves as a signal to initiate blood clotting. This review discusses the determinants and functional implications of the subcellular distribution and membrane topology of PS.

Wanderley JLM, DaMatta RA, Barcinski MA. Apoptotic mimicry as a strategy for the establishment of parasitic infections: parasite- and host-derived phosphatidylserine as key molecule. Cell Commun Signal. 2020 Jan 15;18(1):10. doi: 10.1186/s12964-019-0482-8.

Abstract. The establishment of parasitic infection is dependent on the development of efficient strategies to evade the host defense mechanisms. Phosphatidylserine (PS) molecules are pivotal for apoptotic cell recognition and clearance by professional phagocytes. Moreover, PS receptors are able to trigger anti-inflammatory and immunosuppressive responses by phagocytes, either by coupled enzymes or through the induction of regulatory cytokine secretion. These PS-dependent events are exploited by parasites in a mechanism called apoptotic mimicry. Generally, apoptotic mimicry refers to the effects of PS recognition for the initiation and maintenance of pathogenic infections. However, in this context, PS molecules can be recognized on the surface of the infectious agent or in the surface of apoptotic host debris, leading to the respective denomination of classical and non-classical apoptotic mimicry. In this review, we discuss the role of PS in the pathogenesis of several human infections caused by protozoan parasites.

Bruton A, Nauman J, Hanes D, Gard M, Senders A. Phosphatidylserine for the Treatment of Pediatric Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-Analysis. J Altern Complement Med. 2021 Apr;27(4):312-322. doi: 10.1089/acm.2020.0432. 

Abstract. Objective: To examine the evidence for efficacy of phosphatidylserine for symptoms of attention-deficit/hyperactivity disorder (ADHD) in children. Methods: Medline, Cochrane Library, and ClinicalTrials.gov were searched from inception through August 2020. Studies of any design that assessed phosphatidylserine supplementation for children aged ≤18 years with a diagnosis of ADHD were included in the systematic review; only randomized clinical trials were included in the meta-analysis. Standardized mean differences and 95% confidence intervals (CIs) were calculated, and the heterogeneity of the studies was estimated using I2. The overall quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation tool. Results: Four studies met the inclusion criteria for the narrative review (n = 344) and three for the meta-analysis (n = 216). Results of the meta-analysis showed a statistically significant effect of 200-300 mg/day of phosphatidylserine on symptoms of inattention relative to placebo (effect size [ES] 0.36; 95% CI: 0.07 to 0.64; p = 0.01). The effects of phosphatidylserine on overall symptoms of ADHD (ES 0.76; 95% CI: -0.07 to 1.60; p = 0.07) and hyperactivity-impulsivity (ES 0.24; 95% CI: -0.04 to 0.53; p = 0.09) were not statistically significant. Conclusions: Preliminary evidence suggests that phosphatidylserine may be effective for reducing symptoms of inattention in children with ADHD, although the quality of the evidence is low and additional research in this area is warranted.

Chang W, Fa H, Xiao D, Wang J. Targeting phosphatidylserine for Cancer therapy: prospects and challenges. Theranostics. 2020 Jul 23;10(20):9214-9229. doi: 10.7150/thno.45125. 

Abstract. Cancer is a leading cause of mortality and morbidity worldwide. Despite major improvements in current therapeutic methods, ideal therapeutic strategies for improved tumor elimination are still lacking. Recently, immunotherapy has attracted much attention, and many immune-active agents have been approved for clinical use alone or in combination with other cancer drugs. However, some patients have a poor response to these agents. New agents and strategies are needed to overcome such deficiencies. Phosphatidylserine (PS) is an essential component of bilayer cell membranes and is normally present in the inner leaflet. In the physiological state, PS exposure on the external leaflet not only acts as an engulfment signal for phagocytosis in apoptotic cells but also participates in blood coagulation, myoblast fusion and immune regulation in nonapoptotic cells. In the tumor microenvironment, PS exposure is significantly increased on the surface of tumor cells or tumor cell-derived microvesicles, which have innate immunosuppressive properties and facilitate tumor growth and metastasis. To date, agents targeting PS have been developed, some of which are under investigation in clinical trials as combination drugs for various cancers. However, controversial results are emerging in laboratory research as well as in clinical trials, and the efficiency of PS-targeting agents remains uncertain. In this review, we summarize recent progress in our understanding of the physiological and pathological roles of PS, with a focus on immune suppressive features. In addition, we discuss current drug developments that are based on PS-targeting strategies in both experimental and clinical studies. We hope to provide a future research direction for the development of new agents for cancer therapy. © The author(s).

Kay JG, Fairn GD. Distribution, dynamics and functional roles of phosphatidylserine within the cell. Cell Commun Signal. 2019 Oct 15;17(1):126. doi: 10.1186/s12964-019-0438-z.

Abstract. Phosphatidylserine (PtdSer), an essential constituent of eukaryotic membranes, is the most abundant anionic phospholipid in the eukaryotic cell accounting for up to 10% of the total cellular lipid. Much of what is known about PtdSer is the role exofacial PtdSer plays in apoptosis and blood clotting. However, PtdSer is generally not externally exposed in healthy cells and plays a vital role in several intracellular signaling pathways, though relatively little is known about the precise subcellular localization, transmembrane topology and intracellular dynamics of PtdSer within the cell. The recent development of new, genetically-encoded probes able to detect phosphatidylserine is leading to a more in-depth understanding of the biology of this phospholipid. This review aims to give an overview of recent developments in our understanding of the role of PtdSer in intracellular signaling events derived from the use of these recently developed methods of phosphatidylserine detection.

Stace CL, Ktistakis NT. Phosphatidic acid- and phosphatidylserine-binding proteins. Biochim Biophys Acta. 2006 Aug;1761(8):913-26. doi: 10.1016/j.bbalip.2006.03.006. 

Abstract. Phosphatidic acid and phosphatidylserine are negatively charged abundant phospholipids with well-recognized structural roles in cellular membranes. They are also signaling lipids since their regulated formation (or appearance) can constitute an important signal for downstream responses. The list of potential effectors for these lipids is expanding rapidly and includes proteins involved in virtually all aspects of cellular regulation. Because it is not always clear whether these effectors recognize the specific phospholipids or a general negatively-charged membrane environment, questions about specificity must be addressed on a case by case basis. In this review we present an up to date list of potential phosphatidic acid- and phosphatidylserine-binding proteins.