Phosphatidylserine
 Components of phosphatidylserines: Blue, green: variable fatty acid groups Black: glycerol Red: phosphate Purple: serine | |
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| ChEBI | CHEBI:18303  |
| Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). | |
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Phosphatidylserine (abbreviated Ptd-L-Ser or PS) is an important phospholipid membrane component (i.e. component of the cell membrane) which plays a key role in cell cycle signaling, specifically in relationship to apoptosis.
Cell signaling
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.[1]
Function in Coagulation
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 procoagulant surface. This surface acts to orient coagulation proteases, specifically tissue factor (TF) and Factor VII (the tenase complex), facilitating further proteolysis and activation of Factor X, and ultimately generating thrombin.
The coagulation disorder Scott Syndrome, named for the patient Mary Scott, is caused genetically by mutation for TMEM16F, a scramblase that catalyzes PS externalization. It is characterized as a mild bleeding disorder stemming from the patient's deficiency in thrombin generation.
Supplementation and health benefits
Memory and Cognition
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. FDA concludes that there is little scientific evidence supporting this claim."[2]
The FDA declared that "based on its evaluation of the totality of the publicly available scientific evidence, the agency concludes that there is not significant scientific agreement among qualified experts that a relationship exists between phosphatidylserine and reduced risk of dementia or cognitive dysfunction".[2] The FDA also noted "Of the 10 intervention studies that formed the basis of FDA's evaluation, all were seriously flawed or limited in their reliability in one or more ways", concluding that "most of the evidence does not support a relationship between phosphatidylserine and reduced risk of dementia or cognitive dysfunction, and that the evidence that does support such a relationship is very limited and preliminary".[2]
Early studies of phosphatidylserine on memory and cognition used a supplement which isolated the molecule from the bovine brain. Currently, most commercially available products are made from cabbage or soybeans due to the risk of mad cow disease in bovine brain tissue.[3] These plant-based products have a similar, but not identical chemical structure to the bovine derived supplements; for example, the FDA notes "the phosphatidylserine molecule from soy lecithin contains mainly polyunsaturated acids, while the phosphatidylserine molecule from bovine brain cortex contains mainly saturated and monounsaturated fatty acids and long-chain polyunsaturated fatty acids".[2]
A preliminary study in rats in 1999 indicated that the soy derived phosphatidylserine supplement was as effective as the bovine derived supplement in one of three behavioral tests.[4][5] However, clinical trials in humans found that "a daily supplement of S-PS [soybean-derived phosphatidylserine] does not affect memory or other cognitive functions in older individuals with memory complaints."[6]
Sports nutrition
In athletes, phosphatidylserine has been shown to improve performance,[7][8][9] endocrine response to exercise stress,[10][11] and decrease muscle damage[12] in athletes involved in cycling, weight training, golf and endurance running. PS has been reported to be an effective supplement for combating exercise-induced stress by blunting the exercise-induced increase in cortisol levels in a dose dependent manner.[10][11] PS supplementation promotes a desirable hormonal balance for athletes and might attenuate the physiological deterioration that accompanies overtraining and/or overstretching.[10] In recent studies, PS has been shown to enhance mood in a cohort of young people during mental stress[13] and to improve accuracy during tee-off by increasing the stress resistance of golfers.[9]
Safety
Traditionally, PS supplements were derived from bovine cortex (BC-PS). However, due to the risk of potential transfer of infectious diseases, soy-derived PS (S-PS) supplements have been used as an alternative . Soy-derived PS is designated Generally Recognized As Safe by the FDA. A 2002 safety report determined supplementation in elder people at a dosage of 200 mg three times daily to be safe.[14]
Target for tumor treatment
Bavituximab is a monoclonal antibody directed against phosphatidylserine (PS) expressed on tumor endothelium. Various pathophysiologic processes cause the exposure of PS on the external membrane leaflet. As of 2016 it was in development against several kinds of solid tumors.[15]
Dietary sources
The average daily phosphatidylserine (PS) intake from diet in Western countries is estimated to be 130 mg. 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.
Table 1. PS content in different foods.[16]
| Food | PS Content in mg/100 g |
|---|---|
| Soy lecithin | 5900 [17] |
| 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 |
Metabolism
Phosphatidylserine is biosynthesized in bacteria by condensing the amino acid serine with CDP (cytidine diphosphate)-activated phosphatidic acid.[18] In mammals, phosphatidylserine is produced by base-exchange reactions with phosphatidylcholine and phosphatidylethanolamine. 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.[19]
References
- ↑ Verhoven, B.; Schlegel, R. A.; Williamson, P (1 November 1995). "Mechanisms of phosphatidylserine exposure, a phagocyte recognition signal, on apoptotic T lymphocytes" (PDF). Journal of Experimental Medicine 182 (5): 1597–601. doi:10.1084/jem.182.5.1597. PMC 2192221. PMID 7595231. Retrieved 23 August 2014.
- 1 2 3 4 Taylor, Christine L. (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.
- ↑ Smith, Glenn (2 June 2014). "Can phosphatidylserine improve memory and cognitive function in people with Alzheimer's disease?". Mayo Clinic. Retrieved 23 August 2014.
- ↑ Blokland, A; Honig W; Brouns F; Jolles J (October 1999). "Cognition-enhancing properties of subchronic phosphatidylserine (PS) treatment in middle-aged rats: comparison of bovine cortex PS with egg PS and soybean PS". Nutrition 15 (10): 778–83. doi:10.1016/S0899-9007(99)00157-4. PMID 10501292.
- ↑ Crook, T. H.; R. M. Klatz (ed) (1998). Treatment of Age-Related Cognitive Decline: Effects of Phosphatidylserine in Anti-Aging Medical Therapeutics 2. Chicago: Health Quest Publications. pp. 20–29.
- ↑ 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. PMID 11842880.
- ↑ Kingsley M, Wadsworth D, Kilduff LP, McEneny J, Benton D; Wadsworth; Kilduff; McEneny; Benton (August 2005). "Effects of phosphatidylserine on oxidative stress following intermittent running". Medicine and Science in Sports and Exercise 37 (8): 1300–6. doi:10.1249/01.mss.0000175306.05465.7e. PMID 16118575.
- ↑ Kingsley MI, Miller M, Kilduff LP, McEneny J, Benton D; Miller; Kilduff; McEneny; Benton (January 2006). "Effects of phosphatidylserine on exercise capacity during cycling in active males". Medicine and Science in Sports and Exercise 38 (1): 64–71. doi:10.1249/01.mss.0000183195.10867.d0. PMID 16394955.
- 1 2 Jäger R, Purpura M, Geiss K-R, Weiß M, Baumeister J, Amatulli F, Schröder L, Herwegen H; Purpura; Geiss; Weiß; Baumeister; Amatulli; Schröder; Herwegen (December 2007). "The effect of phosphatidylserine on golf performance". International Society of Sports Nutrition 4 (1): 23. doi:10.1186/1550-2783-4-23. PMC 2217563. PMID 18053194.
- 1 2 3 Starks MA, Starks SL, Kingsley M, Purpura M, Jäger R; Starks; Kingsley; Purpura; Jäger (July 2008). "The effects of phosphatidylserine on endocrine response to moderate intensity exercise". Journal of the International Society of Sports Nutrition 5 (1): 11. doi:10.1186/1550-2783-5-11. PMC 2503954. PMID 18662395.
- 1 2 Monteleone P, Maj M, Beinat L, Natale M, Kemali D; Maj; Beinat; Natale; Kemali (1992). "Blunting by chronic phosphatidylserine administration of the stress-induced activation of the hypothalamo-pituitary-adrenal axis in healthy men". European Journal of Clinical Pharmacology 42 (4): 385–8. doi:10.1007/BF00280123 (inactive 2015-02-01). PMID 1325348.
- ↑ Fernholz KM, Seifert JG, Bacharach DW, Burke ER, Gazal O (2000). "The Effects of Phosphatidyl Serine on Markers of Muscular Stress in Endurance Runners [abstract]". Medicine and Science in Sports and Exercise 32 (4): S321.
- ↑ Benton D, Donohoe RT, Sillance B, Nabb S; Donohoe; Sillance; Nabb (2001). "The Influence of phosphatidylserine supplementation on mood and heart rate when faced with an acute stressor". Nutritional Neuroscience 4 (3): 169–78. PMID 11842886.
- ↑ Jorissen BL, Brouns F, Van Boxtel MP, Riedel WJ; Brouns; Van Boxtel; Riedel (October 2002). "Safety of soy-derived phosphatidylserine in elderly people". Nutritional Neuroscience 5 (5): 337–43. doi:10.1080/1028415021000033802. PMID 12385596.
- ↑ Staff, Adis Insight. Bavituximab profile Last updated Jan 27 2016
- ↑ Souci SW, Fachmann E, Kraut H (2008). Food Composition and Nutrition Tables. Medpharm Scientific Publishers Stuttgart.
- ↑ Scholfield, C.R. (October 1981). "Composition of Soybean Lecithin". Journal of the American Oil Chemists' Society 58 (10): 890. doi:10.1007/bf02659652. Retrieved 23 August 2014.
- ↑ Christie, William W. (4 April 2013). "Phosphatidylserine and Related Lipids: Structure, Occurrence, Biochemistry and Analysis". The American Oil Chemists’ Society Lipid Library. Retrieved 23 August 2014.
- ↑ Christie, William W. (12 June 2014). "Phosphatidylcholine and Related Lipids: Structure, Occurrence, Biochemistry and Analysis". The American Oil Chemists’ Society Lipid Library. Retrieved 23 August 2014.
External links
- DrugBank info page
- FDA Qualified Health Claim Phosphatidylserine and Cognitive Dysfunction and Dementia
- Phosphatidylserines at the US National Library of Medicine Medical Subject Headings (MeSH)
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