phosphatidylserine

Phosphatidylserine is a phospholipid—more specifically a glycerophospholipid—which consists of two fatty acids attached in ester linkage to the first and second carbon of glycerol and serine attached through a phosphodiester linkage to the third carbon of the glycerol.{{Cite book|title=Lehninger Principles of biochemistry|url=https://archive.org/details/lehningerprincip00lehn_596|url-access=limited|last1=Nelson|first1=David|last2=Cox|first2=Michael | name-list-style = vanc |publisher=W.H Freeman and company|year=2008|isbn=9781429208925|edition=5|pages=[https://archive.org/details/lehningerprincip00lehn_596/page/n352 350] }}

Phosphatidylserine sourced from plants differs in fatty acid composition from that sourced from animals.{{Cite journal|last=EFSA Panel on Dietetic Products|first=Nutrition and Allergies|date=2010-10-01|title=Scientific Opinion on the substantiation of health claims related to phosphatidyl serine (ID 552, 711, 734, 1632, 1927) pursuant to Article 13(1) of Regulation (EC) No 1924/2006|journal=EFSA Journal|volume=8|issue=10|pages=1749|doi=10.2903/j.efsa.2010.1749|issn=1831-4732|doi-access=free}} It is commonly found in the inner (cytoplasmic) leaflet of biological membranes.{{Cite book|last1=Nelson|first1=David L.|last2=Cox|first2=Michael M.|last3=Hoskins|first3=Aaron|last4=Lehninger|first4=Albert L.|url=http://worldcat.org/oclc/1249676451|title=Lehninger Principles of Biochemistry|edition=8th|publisher=Macmillan International, Higher Education|publication-place=New York|date=16 March 2021|isbn=978-1-319-38149-3|oclc=1249676451}} It is almost entirely found in the inner monolayer of the membrane with only less than 10% of it in the outer monolayer.{{cn|date=May 2025}}

Phosphatidylserine (PS) is the major acidic phospholipid class that accounts for 13–15% of the phospholipids in the human cerebral cortex. In the plasma membrane, PS is localized exclusively in the cytoplasmic leaflet where it forms part of protein docking sites necessary for the activation of several key signaling pathways. These include the Akt, protein kinase C (PKC) and Raf-1 signaling that is known to stimulate neuronal survival, neurite growth, and synaptogenesis. Modulation of the PS level in the plasma membrane of neurons has a significant impact on these signaling processes.{{cn|date=May 2025}}

Image:Biosynthesis of phosphatidylglycerol, phosphatidylserine, and phosphatidylethanolamine.svg

Phosphatidylserine is formed in bacteria (such as E. coli) through a displacement of cytidine monophosphate (CMP) through a nucleophilic attack by the hydroxyl functional group of serine. CMP is formed from CDP-diacylglycerol by PS synthase. Phosphatidylserine can eventually become phosphatidylethanolamine by the enzyme PS decarboxylase (forming carbon dioxide as a byproduct). Similar to bacteria, yeast can form phosphatidylserine in an identical pathway.{{cn|date=May 2025}}

In mammals, phosphatidylserine is instead derived from phosphatidylethanolamine or phosphatidylcholine through one of two Ca²⁺-dependent head-group exchange reactions in the endoplasmic reticulum. Both reactions require a serine but produce an ethanolamine or choline, respectively. These are promoted by phosphatidylserine synthase 1 (PSS1) or 2 (PSS2). Conversely, phosphatidylserine can also give rise to phosphatidylethanolamine and phosphatidylcholine, although in animals the pathway to generate phosphatidylcholine from phosphatidylserine only operates in the liver.{{cite web|last1=Christie|first1=William W.|name-list-style=vanc|date=12 June 2014|title=Phosphatidylcholine and Related Lipids: Structure, Occurrence, Biochemistry and Analysis|url=http://aocs.files.cms-plus.com/LipidsLibrary/images/Importedfiles/lipidlibrary/Lipids/pc/file.pdf|access-date=20 April 2017|website=The American Oil Chemists' Society Lipid Library}}

PS has been studied for its potential in improving memory, learning, and concentration. Supplementation with PS has been shown to have no effect in enhancing cognitive performance in the elderly and individuals with cognitive decline.{{Cite journal |last1=Jorissen |first1=B.L. |last2=Brouns |first2=F. |last3=Van Boxtel |first3=M.P.J. |last4=Ponds |first4=R.W.H.M. |last5=Verhey |first5=F.R.J. |last6=Jolles |first6=J. |last7=Riedel |first7=W.J. |date=January 2001 |title=The Influence of Soy-derived Phosphatidylserine on Cognition in Age-Associated Memory Impairment |url=http://dx.doi.org/10.1080/1028415x.2001.11747356 |journal=Nutritional Neuroscience |volume=4 |issue=2 |pages=121–134 |doi=10.1080/1028415x.2001.11747356 |pmid=11842880 |issn=1028-415X}}

PS plays a crucial role in the process of apoptosis (programmed cell death). During apoptosis, PS translocates from the inner leaflet of the cell membrane to the outer leaflet, serving as a signal for phagocytic cells to engulf the dying cell.{{Cite journal |last1=Fadok |first1=V A |last2=Voelker |first2=D R |last3=Campbell |first3=P A |last4=Cohen |first4=J J |last5=Bratton |first5=D L |last6=Henson |first6=P M |date=1992-04-01 |title=Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages. |url=http://dx.doi.org/10.4049/jimmunol.148.7.2207 |journal=The Journal of Immunology |volume=148 |issue=7 |pages=2207–2216 |doi=10.4049/jimmunol.148.7.2207 |issn=0022-1767}}

The average daily phosphatidylserine intake in a Western diet is estimated to be 130{{thinsp}}mg.Souci SW, Fachmann E, Kraut H: Food Composition and Nutrition Tables. Stuttgart. 2000, Medpharm Scientific Publishers Phosphatidylserine may be found in meat and fish. Only small amounts are found in dairy products and vegetables, with the exception of white beans and soy lecithin. Phosphatidylserine is found in soy lecithin at about 3% of total phospholipids.{{Cite journal|last1=Miranda|first1=Dalva T. S. Z.|last2=Batista|first2=Vanessa G.|last3=Grando|first3=Fernanda C. C.|last4=Paula|first4=Fernanda M.|last5=Felício|first5=Caroline A.|last6=Rubbo|first6=Gabriella F. S.|last7=Fernandes|first7=Luiz C.|last8=Curi|first8=Rui|last9=Nishiyama|first9=Anita|date=Dec 2008|title=Soy lecithin supplementation alters macrophage phagocytosis and lymphocyte response to concanavalin A: a study in alloxan-induced diabetic rats|journal=Cell Biochemistry and Function|volume=26|issue=8|pages=859–865|doi=10.1002/cbf.1517|issn=1099-0844|pmid=18846580|s2cid=9083077}}

Table 1. Phosphatidylserine content in different foods.{{cite book |vauthors=Souci SW, Fachmann E, Kraut H | year=2008 | title=Food Composition and Nutrition Tables. Medpharm Scientific Publishers Stuttgart}}

A panel of the European Food Safety Authority concluded that a cause and effect relationship cannot be established between the consumption of phosphatidylserine and "memory and cognitive functioning in the elderly", "mental health/cognitive function" and "stress reduction and enhanced memory function". This conclusion follows because bovine brain cortex- and soy-based phosphatidylserine are different substances and might, therefore, have different biological activities. Therefore, the results of studies using phosphatidylserine from different sources cannot be generalized.

In May, 2003 the Food and Drug Administration gave "qualified health claim" status to phosphatidylserine thus allowing labels to state "consumption of phosphatidylserine may reduce the risk of dementia and cognitive dysfunction in the elderly" along with the disclaimer "very limited and preliminary scientific research suggests that phosphatidylserine may reduce the risk of cognitive dysfunction in the elderly."{{cite web|url=https://www.fda.gov/food/ingredientspackaginglabeling/labelingnutrition/ucm072999.htm |archive-url=https://web.archive.org/web/20130619104745/http://www.fda.gov/Food/IngredientsPackagingLabeling/LabelingNutrition/ucm072999.htm |url-status=dead |archive-date=June 19, 2013 |title=Phosphatidylserine and Cognitive Dysfunction and Dementia (Qualified Health Claim: Final Decision Letter) |last=Taylor |first=Christine L. | name-list-style = vanc |publisher=Center for Food Safety and Applied Nutrition, U.S. Food and Drug Administration |date=May 13, 2003 |access-date=23 August 2014}}{{Cite web|url=https://www.fda.gov/Food/IngredientsPackagingLabeling/LabelingNutrition/ucm073992.htm#cognitive|archive-url=https://web.archive.org/web/20130610003617/http://www.fda.gov/Food/IngredientsPackagingLabeling/LabelingNutrition/ucm073992.htm#cognitive|url-status=dead|archive-date=June 10, 2013|title=Summary of Qualified Health Claims Subject to Enforcement Discretion - Qualified Claims About Cognitive Function|website=Food and Drug Administration }}{{citation needed|date=December 2024}}{{Failed verification|date=December 2024}} According to the FDA, there is a lack of scientific agreement amongst qualified experts that a relationship exists between phosphatidylserine and cognitive function.

More recent reviews have suggested that the relationship may be more robust,{{cite journal | vauthors = Glade MJ, Smith K | title = Phosphatidylserine and the human brain | journal = Nutrition | volume = 31 | issue = 6 | pages = 781–6 | date = June 2015 | pmid = 25933483 | doi = 10.1016/j.nut.2014.10.014 }}{{better source needed|date=December 2024}}{{cite journal|last1=Poddar|first1=Jit|last2=Pradhan|first2=Munmun|last3=Ganguly|first3=Gargi|last4=Chakrabarti|first4=Sasanka|title=Biochemical deficits and cognitive decline in brain aging: Intervention by dietary supplements|journal=Journal of Chemical Neuroanatomy|volume=95|year=2019|pages=70–80|issn=0891-0618|doi=10.1016/j.jchemneu.2018.04.002|pmid=29678666|s2cid=5014367}}{{Failed verification|date=December 2024}} though the mechanism remains unclear.{{cite journal | vauthors = Kim HY, Huang BX, Spector AA | title = Phosphatidylserine in the brain: metabolism and function | journal = Progress in Lipid Research | volume = 56 | pages = 1–18 | date = October 2014 | pmid = 24992464 | pmc = 4258547 | doi = 10.1016/j.plipres.2014.06.002 }} A 2020 review of three clinical trials found that phosphatidylserine is likely effective for enhancing cognitive function in older people with mild cognitive impairment.{{Cite web|last=Tardner|first=P.|date=2020-08-28|title=The effects of phosphatidylserine supplementation on memory function in older people: A review of clinical literature • International Journal of Environmental Science & Technology|url=https://www.ijest.org/phosphatidylserine-memory-older-people-ptardner0820/|access-date=2020-09-01|website=International Journal of Environmental Science & Technology|language=en-US}}{{Failed verification|date=December 2024}}{{better source needed|date=December 2024}} Some studies have suggested that whether the phosphatidylserine is plant- or animal-derived may have significance, with the FDA's statement applying specifically to soy-derived products.{{cite web|last1=Smith|first1=Glenn|title=Can phosphatidylserine improve memory and cognitive function in people with Alzheimer's disease?|url=http://www.mayoclinic.org/diseases-conditions/alzheimers-disease/expert-answers/phosphatidylserine/faq-20057764|website=Mayo Clinic|access-date=23 August 2014|date=2 June 2014}}{{Failed verification|date=December 2024}}{{cite book |title=Treatment of Age-Related Cognitive Decline: Effects of Phosphatidylserine in Anti-Aging Medical Therapeutics | veditors = Crook TH, Klatz RM | volume=2 | publisher = Health Quest Publications | location=Chicago | year=1998 | pages=20–29}}{{cite journal | vauthors = Jorissen BL, Brouns F, Van Boxtel MP, Ponds RW, Verhey FR, Jolles J, Riedel WJ | title = The influence of soy-derived phosphatidylserine on cognition in age-associated memory impairment | journal = Nutritional Neuroscience | volume = 4 | issue = 2 | pages = 121–34 | year = 2001 | pmid = 11842880 | url = http://arno.unimaas.nl/show.cgi?fid=4834 | doi = 10.1080/1028415X.2001.11747356 | s2cid = 9426593 | access-date = 2014-08-23 | archive-url = https://web.archive.org/web/20140826160810/http://arno.unimaas.nl/show.cgi?fid=4834 | archive-date = 2014-08-26 | url-status = dead }}{{cite journal | vauthors = Kato-Kataoka A, Sakai M, Ebina R, Nonaka C, Asano T, Miyamori T | title = Soybean-derived phosphatidylserine improves memory function of the elderly Japanese subjects with memory complaints | journal = Journal of Clinical Biochemistry and Nutrition | volume = 47 | issue = 3 | pages = 246–55 | date = November 2010 | pmid = 21103034 | pmc = 2966935 | doi = 10.3164/jcbn.10-62 }}

Initially, phosphatidylserine supplements were derived from bovine cortex. However, due to the risk of potential transfer of infectious diseases such as bovine spongiform encephalopathy (or "mad cow disease"), soy-derived supplements became an alternative. A 2002 safety report determined supplementation in elderly people at a dosage of 200{{thinsp}}mg three times daily to be safe.{{cite journal | vauthors = Jorissen BL, Brouns F, Van Boxtel MP, Riedel WJ | title = Safety of soy-derived phosphatidylserine in elderly people | journal = Nutritional Neuroscience | volume = 5 | issue = 5 | pages = 337–43 | date = October 2002 | pmid = 12385596 | doi = 10.1080/1028415021000033802 | s2cid = 5688203 }} Some manufacturers of phosphatidylserine use sunflower lecithin instead of soy lecithin as a source of raw material production.{{cn|date=May 2025}}

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• [https://go.drugbank.com/drugs/DB00144 DrugBank info page]
• {{MeshName|Phosphatidylserines}}

{{Phospholipids}}

Category:Phospholipids

Category:Membrane biology