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Phosphatidylserine

Phosphatidylserine (abbreviated Ptd-L-Ser or PS) is a phospholipid and is a component of the cell membrane.[1] It plays a key role in cell cycle signaling, specifically in relation to apoptosis. It is a key pathway for viruses to enter cells via apoptotic mimicry.[2]

Phosphatidylserine
Phosphatidyl-Serine.png
Components of phosphatidylserines:
Blue, green: variable fatty acid groups
Black: glycerol
Red: phosphate
Purple: serine
Identifiers
ChEBI
ChemSpider
  • none
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

StructureEdit

Phosphatidylserine is a phospholipid (more specifically a glycerophospholipid). It 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.[3]

Phosphatidylserine coming from plants and phosphatidylserine coming from animals differ in fatty acid composition.[4]

Biological functionEdit

Cell signalingEdit

Phosphatidylserine(s) are actively held facing the cytosolic (inner) side of the cell membrane by the enzyme flippase. However, when a cell undergoes apoptosis, phosphatidylserine is no longer restricted to the cytosolic side by flippase. Instead scramblase catalyzes the rapid exchange of phosphatidylserine between the two sides. When the phosphatidylserines flip to the extracellular (outer) surface of the cell, they act as a signal for macrophages to engulf the cells.[5]

CoagulationEdit

Phosphatidylserine plays a role in blood coagulation (also known as clotting). When circulating platelets encounter the site of an injury, collagen and thrombin-mediated activation causes externalization of phosphatidylserine (PS) from the inner membrane layer, where it serves as a pro-coagulant surface.[6] This surface acts to orient coagulation proteases, specifically tissue factor (TF) and factor VII, facilitating further proteolysis, activation of factor X, and ultimately generating thrombin.[6]

In the coagulation disorder Scott syndrome, the mechanism in platelets for transportation of PS from the inner platelet membrane surface to the outer membrane surface is defective.[7] It is characterized as a mild bleeding disorder stemming from the patient's deficiency in thrombin synthesis.[8]

BiosynthesisEdit

 
Biosynthesis of phosphatidylserine

Phosphatidylserine is biosynthesized in bacteria by condensing the amino acid serine with CDP (cytidine diphosphate)-activated phosphatidic acid.[9] In mammals, phosphatidylserine is produced by base-exchange reactions with phosphatidylcholine and phosphatidylethanolamine.[10] 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.[11]

Dietary sourcesEdit

The average daily phosphatidylserine (PS) intake from diet in Western countries is estimated to be 130 mg.[12] PS may be found in meat and fish. Only small amounts of PS can be found in dairy products or in vegetables, with the exception of white beans and soy lecithin. PS is found in soy lecithin at about 3% of total phospholipids.[13]

Table 1. PS content in different foods.[14] Soy products are not in this table, because commercial PS is made by enzymatically converting soy phosphatidylcholine (lecithin) to phosphatidylserine, rather than purifying phosphatidylserine from soy.[citation needed]

Food PS Content in mg/100 g
Bovine brain 713
Atlantic mackerel 480
Chicken heart 414
Atlantic herring 360
Eel 335
Offal (average value) 305
Pig's spleen 239
Pig's kidney 218
Tuna 194
Chicken leg, with skin, without bone 134
Chicken liver 123
White beans 107
Soft-shell clam 87
Chicken breast, with skin 85
Mullet 76
Veal 72
Beef 69
Pork 57
Pig's liver 50
Turkey leg, without skin or bone 50
Turkey breast without skin 45
Crayfish 40
Cuttlefish 31
Atlantic cod 28
Anchovy 25
Whole grain barley 20
European hake 17
European pilchard (sardine) 16
Trout 14
Rice (unpolished) 3
Carrot 2
Ewe's Milk 2
Cow's Milk (whole, 3.5% fat) 1
Potato 1

SupplementationEdit

Health claimsEdit

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”.[4] The reason is that bovine brain cortex- and soy-based phosphatidylserine are different substances and might, therefore, have different biological activities. Therefore, the results of studies using PS coming from different sources cannot be generalized.[4]

CognitionEdit

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."[15][16] According to the FDA, there is a lack of scientific agreement amongst qualified experts that a relationship exists between phosphatidylserine and cognitive function.[15]

More recent reviews have suggested that the relationship may be more robust,[17][18] though the mechanism remains unclear.[19] 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.[15][20][21][22][23]

SafetyEdit

Traditionally, PS supplements were derived from bovine cortex (BC-PS). However, due to the risk of potential transfer of infectious diseases such as bovine spongiform encephalopathy (or "mad cow disease"), soy-derived PS supplements have been used as an alternative.[20] Soy-derived PS is designated Generally Recognized As Safe by the FDA.[citation needed] A 2002 safety report determined supplementation in elder people at a dosage of 200 mg three times daily to be safe.[24] Even so, concerns about the safety of soy products persist, and some manufacturers of PS use sunflower lecithin instead of soy lecithin as a source of raw material for PS production.

ReferencesEdit

  1. ^ Kannan, Muthukumar; Riekhof, Wayne R.; Voelker, Dennis R. (2015). "Transport of Phosphatidylserine from the Endoplasmic Reticulum to the Site of Phosphatidylserine Decarboxylase2 in Yeast". Traffic. 16 (2): 123–134. doi:10.1111/tra.12236. ISSN 1600-0854. PMID 25355612.
  2. ^ Meertens L, Carnec X, Lecoin MP, Ramdasi R, Guivel-Benhassine F, Lew E, Lemke G, Schwartz O, Amara A (October 2012). "The TIM and TAM families of phosphatidylserine receptors mediate dengue virus entry". Cell Host & Microbe. 12 (4): 544–57. doi:10.1016/j.chom.2012.08.009. PMC 3572209. PMID 23084921.
  3. ^ Nelson D, Cox M (2008). Lehninger Principles of biochemistry (5 ed.). W.H Freeman and company. p. 350. ISBN 9781429208925.
  4. ^ a b c EFSA Panel on Dietetic Products, Nutrition and Allergies (2010-10-01). "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". EFSA Journal. 8 (10): 1749. doi:10.2903/j.efsa.2010.1749. ISSN 1831-4732.
  5. ^ Verhoven B, Schlegel RA, Williamson P (November 1995). "Mechanisms of phosphatidylserine exposure, a phagocyte recognition signal, on apoptotic T lymphocytes". The Journal of Experimental Medicine. 182 (5): 1597–601. doi:10.1084/jem.182.5.1597. PMC 2192221. PMID 7595231.
  6. ^ a b Lentz BR (September 2003). "Exposure of platelet membrane phosphatidylserine regulates blood coagulation". Progress in Lipid Research. 42 (5): 423–38. doi:10.1016/s0163-7827(03)00025-0. PMID 12814644.
  7. ^ Zwaal RF, Comfurius P, Bevers EM (March 2004). "Scott syndrome, a bleeding disorder caused by defective scrambling of membrane phospholipids". Biochimica et Biophysica Acta. 1636 (2–3): 119–28. doi:10.1016/j.bbalip.2003.07.003. PMID 15164759.
  8. ^ Weiss HJ (October 1994). "Scott syndrome: a disorder of platelet coagulant activity". Seminars in Hematology. 31 (4): 312–9. PMID 7831576.
  9. ^ Christie WW (4 April 2013). "Phosphatidylserine and Related Lipids: Structure, Occurrence, Biochemistry and Analysis" (PDF). The American Oil Chemists’ Society Lipid Library. Retrieved 20 April 2017.
  10. ^ Kannan, Muthukumar; Riekhof, Wayne R.; Voelker, Dennis R. (2015). "Transport of Phosphatidylserine from the Endoplasmic Reticulum to the Site of Phosphatidylserine Decarboxylase2 in Yeast". Traffic. 16 (2): 123–134. doi:10.1111/tra.12236. ISSN 1600-0854. PMID 25355612.
  11. ^ Christie WW (12 June 2014). "Phosphatidylcholine and Related Lipids: Structure, Occurrence, Biochemistry and Analysis" (PDF). The American Oil Chemists’ Society Lipid Library. Retrieved 20 April 2017.
  12. ^ Souci SW, Fachmann E, Kraut H: Food Composition and Nutrition Tables. Stuttgart. 2000, Medpharm Scientific Publishers
  13. ^ Miranda, Dalva T. S. Z.; Batista, Vanessa G.; Grando, Fernanda C. C.; Paula, Fernanda M.; Felício, Caroline A.; Rubbo, Gabriella F. S.; Fernandes, Luiz C.; Curi, Rui; Nishiyama, Anita (Dec 2008). "Soy lecithin supplementation alters macrophage phagocytosis and lymphocyte response to concanavalin A: a study in alloxan-induced diabetic rats". Cell Biochemistry and Function. 26 (8): 859–865. doi:10.1002/cbf.1517. ISSN 1099-0844. PMID 18846580.
  14. ^ Souci SW, Fachmann E, Kraut H (2008). Food Composition and Nutrition Tables. Medpharm Scientific Publishers Stuttgart.
  15. ^ a b c Taylor CL (May 13, 2003). "Phosphatidylserine and Cognitive Dysfunction and Dementia (Qualified Health Claim: Final Decision Letter)". Center for Food Safety and Applied Nutrition, U.S. Food and Drug Administration. Retrieved 23 August 2014.
  16. ^ "Summary of Qualified Health Claims Subject to Enforcement Discretion - Qualified Claims About Cognitive Function".
  17. ^ Glade MJ, Smith K (June 2015). "Phosphatidylserine and the human brain". Nutrition. 31 (6): 781–6. doi:10.1016/j.nut.2014.10.014. PMID 25933483.
  18. ^ Poddar, Jit; Pradhan, Munmun; Ganguly, Gargi; Chakrabarti, Sasanka (2019). "Biochemical deficits and cognitive decline in brain aging: Intervention by dietary supplements". Journal of Chemical Neuroanatomy. 95: 70–80. doi:10.1016/j.jchemneu.2018.04.002. ISSN 0891-0618.
  19. ^ Kim HY, Huang BX, Spector AA (October 2014). "Phosphatidylserine in the brain: metabolism and function". Progress in Lipid Research. 56: 1–18. doi:10.1016/j.plipres.2014.06.002. PMC 4258547. PMID 24992464.
  20. ^ a b Smith, Glenn (2 June 2014). "Can phosphatidylserine improve memory and cognitive function in people with Alzheimer's disease?". Mayo Clinic. Retrieved 23 August 2014.
  21. ^ Crook TH, Klatz RM, eds. (1998). Treatment of Age-Related Cognitive Decline: Effects of Phosphatidylserine in Anti-Aging Medical Therapeutics. 2. Chicago: Health Quest Publications. pp. 20–29.
  22. ^ Jorissen BL, Brouns F, Van Boxtel MP, Ponds RW, Verhey FR, Jolles J, Riedel WJ (2001). "The influence of soy-derived phosphatidylserine on cognition in age-associated memory impairment". Nutritional Neuroscience. 4 (2): 121–34. doi:10.1080/1028415X.2001.11747356. PMID 11842880.
  23. ^ Kato-Kataoka A, Sakai M, Ebina R, Nonaka C, Asano T, Miyamori T (November 2010). "Soybean-derived phosphatidylserine improves memory function of the elderly Japanese subjects with memory complaints". Journal of Clinical Biochemistry and Nutrition. 47 (3): 246–55. doi:10.3164/jcbn.10-62. PMC 2966935. PMID 21103034.
  24. ^ Jorissen BL, Brouns F, Van Boxtel MP, Riedel WJ (October 2002). "Safety of soy-derived phosphatidylserine in elderly people". Nutritional Neuroscience. 5 (5): 337–43. doi:10.1080/1028415021000033802. PMID 12385596.

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