You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NamePhosphatidylserine
Accession NumberDB00144  (NUTR00048)
Typesmall molecule
Groupsapproved, nutraceutical
Description

Phosphatidylserine (PS) is a phospholipid nutrient found in fish, green leafy vegetables, soybeans and rice, and is essential for the normal functioning of neuronal cell membranes and activates Protein kinase C (PKC) which has been shown to be involved in memory function. In apoptosis, phosphatidylserine is transferred to the outer leaflet of the plasma membrane. This is part of the process by which the cell is targeted for phagocytosis. PS has been shown to slow cognitive decline in animal models. PS has been investigated in a small number of double-blind placebo trials and has been shown to increase memory performance in the elderly. Because of the potentail cognitive benefits of phosphatidylserine, the substance is sold as a dietary supplement to people who believe they can benefit from an increased intake.

The dietary supplement was originally processed from bovine sources however Prion disease scares in the 1990s outlawed this process, and a soy-based alternative was adopted.

Structure
Thumb
Synonyms
SynonymLanguageCode
Phosphatidyl-L-serineNot AvailableNot Available
PSNot AvailableNot Available
Ptd-L-SerNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
LifeExtension PS CapsNot Available
Brand mixturesNot Available
Categories
CAS number8002-43-5
WeightAverage: 385.3041
Monoisotopic: 385.113782505
Chemical FormulaC13H24NO10P
InChI KeyUNJJBGNPUUVVFQ-ZJUUUORDSA-N
InChI
InChI=1S/C13H24NO10P/c1-3-5-12(16)24-9(6-21-11(15)4-2)7-22-25(19,20)23-8-10(14)13(17)18/h9-10H,3-8,14H2,1-2H3,(H,17,18)(H,19,20)/t9-,10+/m1/s1
IUPAC Name
(2S)-2-amino-3-({[(2R)-2-(butanoyloxy)-3-(propanoyloxy)propoxy](hydroxy)phosphoryl}oxy)propanoic acid
SMILES
CCCC(=O)O[C@H](COC(=O)CC)COP(O)(=O)OC[C@H](N)C(O)=O
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassLipids
ClassGlycerophospholipids
SubclassGlycerophosphoserines
Direct parentPhosphatidylserines
Alternative parentsAlpha Amino Acids and Derivatives; Tricarboxylic Acids and Derivatives; Phosphoethanolamines; Organic Phosphoric Acids; Carboxylic Acid Esters; Ethers; Enolates; Carboxylic Acids; Polyamines; Monoalkylamines
Substituentsalpha-amino acid or derivative; tricarboxylic acid derivative; phosphoethanolamine; phosphoric acid ester; organic phosphate; carboxylic acid ester; polyamine; enolate; carboxylic acid; carboxylic acid derivative; ether; primary amine; primary aliphatic amine; amine; organonitrogen compound
Classification descriptionThis compound belongs to the phosphatidylserines. These are glycerophosphoserines in which two fatty acids are bonded to the glycerol moiety through ester linkages.
Pharmacology
IndicationPhosphatidylserine has demonstrated some usefulness in treating cognitive impairment, including Alzheimer's disease, age-associated memory impairment and some non-Alzheimer's dementias. More research is needed before phosphatidylserine can be indicated for immune enhancement or for reduction of exercise stress.
PharmacodynamicsPhosphatidylserine is indicated in the treatment of cognitive impairment, including Alzheimer's disease, age-associated memory impairment and some non-Alzheimer's dementias. Further research is required before phosphatidylserine can be indicated for immune enhancement or for reduction of exercise stress. Phosphatidylserine was first isolated from brain lipids called cephalins. The major cephalins are phosphatidylserine and phophatidylethanolamine. Phosphatidylserine is involved in signal transduction activity as well as being a basic structural component of biologic membranes.
Mechanism of actionCholinergic hypofunction is thought to account in part for the cognitive deficits found in Alzheimer's disease. The most commonly used drugs for the treatment of Alzheimer's disease are reversible acetylcholinesterase inhibitors. The rationale of these drugs is to increase acetylcholine levels in the brains of Alzheimer's patients, and they may be somewhat effective in some cases. Phosphatidylserine restores acetylcholine release in aging humans by maintaining an adequate supply of the molecule and is able to increase the availability of endogenous choline for de novo acetylcholine synthesis. The hippocampus of the brain is believed to be important for cognitive processes and is affected in those with Alzheimer's disease. The dendritic spines of pyramidal cells, the post-synaptic target of the excitatory input to the hippocampus, have been proposed as a substrate for information storage. Age-dependent dendritic spine loss in pyramidal neurons has been reported in the human brain, and the extent of synaptic loss appears to correlate with the degree of cognitive impairment. Phosphatidylserine treatment prevents the age-related reduction in dendritic spine density in rat hippocampus. Protein kinase C facilitation of acetylcholine release has been reported in rats. Phosphatidylserine was found to restore protein kinase C activity in aging rats. Stimulation of calcium uptake by brain synaptosomes and activation of protein kinase C are yet other speculative mechanisms of phosphatidylserine's putative cognition-enhancing action.
AbsorptionAbsorbed in the small intestine.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Following absorption, lysophosphatidylserine is metabolized in intestinal mucosa cells, and its metabolites, which include some phosphatidylserine, enter the lymphatics draining the small intestine.

Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityThere are no reports of overdosage. LD50 in rats is more than 5g/kg, and in rabbits is more than 2g/kg.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption - 0.6612
Blood Brain Barrier + 0.5475
Caco-2 permeable - 0.666
P-glycoprotein substrate Non-substrate 0.5358
P-glycoprotein inhibitor I Non-inhibitor 0.7716
P-glycoprotein inhibitor II Non-inhibitor 0.9679
Renal organic cation transporter Non-inhibitor 0.9512
CYP450 2C9 substrate Non-substrate 0.9229
CYP450 2D6 substrate Non-substrate 0.8056
CYP450 3A4 substrate Non-substrate 0.6063
CYP450 1A2 substrate Non-inhibitor 0.7648
CYP450 2C9 substrate Non-inhibitor 0.8731
CYP450 2D6 substrate Non-inhibitor 0.8662
CYP450 2C19 substrate Non-inhibitor 0.7588
CYP450 3A4 substrate Non-inhibitor 0.7248
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9716
Ames test Non AMES toxic 0.7626
Carcinogenicity Non-carcinogens 0.7671
Biodegradation Not ready biodegradable 0.7036
Rat acute toxicity 2.1996 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9279
hERG inhibition (predictor II) Non-inhibitor 0.7921
Pharmacoeconomics
ManufacturersNot Available
Packagers
  • Professional Co.
Dosage formsNot Available
Prices
Unit descriptionCostUnit
Phosphatidylserine 40% powder13.2USDg
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
logP-3.5Not Available
Predicted Properties
PropertyValueSource
water solubility3.70e+00 g/lALOGPS
logP-1ALOGPS
logP-1.6ChemAxon
logS-2ALOGPS
pKa (strongest acidic)1.47ChemAxon
pKa (strongest basic)9.38ChemAxon
physiological charge-1ChemAxon
hydrogen acceptor count7ChemAxon
hydrogen donor count3ChemAxon
polar surface area171.68ChemAxon
rotatable bond count15ChemAxon
refractivity81.81ChemAxon
polarizability35.58ChemAxon
number of rings0ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Lorenzo De Ferra, Pietro Massardo, Oreste Piccolo, Stefano Servi, “Process for the industrial preparation of phosphatidylserine.” U.S. Patent US5700668, issued January, 1992.

US5700668
General ReferenceNot Available
External Links
ResourceLink
PubChem Compound6323481
PubChem Substance46505650
ChemSpider13628254
ChEBI18303
ChEMBL
PharmGKBPA164768860
IUPHAR3638
Guide to Pharmacology3638
HETPSF
PDRhealthhttp://www.pdrhealth.com/drug_info/nmdrugprofiles/nutsupdrugs/pho_0202.shtml
WikipediaPhosphatidylserine
ATC CodesNot Available
AHFS CodesNot Available
PDB Entries
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. Diacylglycerol kinase gamma

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Diacylglycerol kinase gamma P49619 Details

References:

  1. Yamaguchi Y, Shirai Y, Matsubara T, Sanse K, Kuriyama M, Oshiro N, Yoshino K, Yonezawa K, Ono Y, Saito N: Phosphorylation and up-regulation of diacylglycerol kinase gamma via its interaction with protein kinase C gamma. J Biol Chem. 2006 Oct 20;281(42):31627-37. Epub 2006 Aug 11. Pubmed

2. Diacylglycerol kinase delta

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Diacylglycerol kinase delta Q16760 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Bregoli L, Baldassare JJ, Raben DM: Nuclear diacylglycerol kinase-theta is activated in response to alpha-thrombin. J Biol Chem. 2001 Jun 29;276(26):23288-95. Epub 2001 Apr 17. Pubmed
  4. Sakane F, Imai S, Kai M, Wada I, Kanoh H: Molecular cloning of a novel diacylglycerol kinase isozyme with a pleckstrin homology domain and a C-terminal tail similar to those of the EPH family of protein-tyrosine kinases. J Biol Chem. 1996 Apr 5;271(14):8394-401. Pubmed

3. Phosphatidylserine synthase 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Phosphatidylserine synthase 2 Q9BVG9 Details

References:

  1. Bergo MO, Gavino BJ, Steenbergen R, Sturbois B, Parlow AF, Sanan DA, Skarnes WC, Vance JE, Young SG: Defining the importance of phosphatidylserine synthase 2 in mice. J Biol Chem. 2002 Dec 6;277(49):47701-8. Epub 2002 Oct 1. Pubmed
  2. Vance JE, Vance DE: Phospholipid biosynthesis in mammalian cells. Biochem Cell Biol. 2004 Feb;82(1):113-28. Pubmed
  3. Dygas A, Baranska J, Santella L: Ca2+-dependent phosphatidylserine synthesis in immature and mature starfish oocytes. Acta Biochim Pol. 2003;50(2):377-87. Pubmed
  4. Grandmaison PA, Nanowski TS, Vance JE: Externalization of phosphatidylserine during apoptosis does not specifically require either isoform of phosphatidylserine synthase. Biochim Biophys Acta. 2004 Feb 27;1636(1):1-11. Pubmed
  5. Wen Z, Kim HY: Inhibition of phosphatidylserine biosynthesis in developing rat brain by maternal exposure to ethanol. J Neurosci Res. 2007 May 15;85(7):1568-78. Pubmed

4. Sphingomyelin phosphodiesterase 4

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Sphingomyelin phosphodiesterase 4 Q9NXE4 Details

References:

  1. Krut O, Wiegmann K, Kashkar H, Yazdanpanah B, Kronke M: Novel tumor necrosis factor-responsive mammalian neutral sphingomyelinase-3 is a C-tail-anchored protein. J Biol Chem. 2006 May 12;281(19):13784-93. Epub 2006 Mar 3. Pubmed

5. Sphingomyelin phosphodiesterase 3

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Sphingomyelin phosphodiesterase 3 Q9NY59 Details

References:

  1. Krut O, Wiegmann K, Kashkar H, Yazdanpanah B, Kronke M: Novel tumor necrosis factor-responsive mammalian neutral sphingomyelinase-3 is a C-tail-anchored protein. J Biol Chem. 2006 May 12;281(19):13784-93. Epub 2006 Mar 3. Pubmed
  2. Marchesini N, Luberto C, Hannun YA: Biochemical properties of mammalian neutral sphingomyelinase 2 and its role in sphingolipid metabolism. J Biol Chem. 2003 Apr 18;278(16):13775-83. Epub 2003 Feb 3. Pubmed

6. Probable phospholipid-transporting ATPase IA

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Probable phospholipid-transporting ATPase IA Q9Y2Q0 Details

References:

  1. Bettache N, Baisamy L, Baghdiguian S, Payrastre B, Mangeat P, Bienvenue A: Mechanical constraint imposed on plasma membrane through transverse phospholipid imbalance induces reversible actin polymerization via phosphoinositide 3-kinase activation. J Cell Sci. 2003 Jun 1;116(Pt 11):2277-84. Epub 2003 Apr 15. Pubmed
  2. Wolfs JL, Comfurius P, Rasmussen JT, Keuren JF, Lindhout T, Zwaal RF, Bevers EM: Activated scramblase and inhibited aminophospholipid translocase cause phosphatidylserine exposure in a distinct platelet fraction. Cell Mol Life Sci. 2005 Jul;62(13):1514-25. Pubmed
  3. Mandal D, Mazumder A, Das P, Kundu M, Basu J: Fas-, caspase 8-, and caspase 3-dependent signaling regulates the activity of the aminophospholipid translocase and phosphatidylserine externalization in human erythrocytes. J Biol Chem. 2005 Nov 25;280(47):39460-7. Epub 2005 Sep 22. Pubmed
  4. Paterson JK, Renkema K, Burden L, Halleck MS, Schlegel RA, Williamson P, Daleke DL: Lipid specific activation of the murine P4-ATPase Atp8a1 (ATPase II). Biochemistry. 2006 Apr 25;45(16):5367-76. Pubmed

7. Protein kinase C alpha type

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Protein kinase C alpha type P17252 Details

References:

  1. Yu D, Kazanietz MG, Harvey RG, Penning TM: Polycyclic aromatic hydrocarbon o-quinones inhibit the activity of the catalytic fragment of protein kinase C. Biochemistry. 2002 Oct 1;41(39):11888-94. Pubmed
  2. Rodriguez-Alfaro JA, Gomez-Fernandez JC, Corbalan-Garcia S: Role of the lysine-rich cluster of the C2 domain in the phosphatidylserine-dependent activation of PKCalpha. J Mol Biol. 2004 Jan 23;335(4):1117-29. Pubmed
  3. Lopez-Andreo MJ, Torrecillas A, Conesa-Zamora P, Corbalan-Garcia S, Gomez-Fernandez JC: Retinoic acid as a modulator of the activity of protein kinase Calpha. Biochemistry. 2005 Aug 30;44(34):11353-60. Pubmed
  4. Corbin JA, Evans JH, Landgraf KE, Falke JJ: Mechanism of specific membrane targeting by C2 domains: localized pools of target lipids enhance Ca2+ affinity. Biochemistry. 2007 Apr 10;46(14):4322-36. Epub 2007 Mar 17. Pubmed

8. Phosphatidylserine synthase 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Phosphatidylserine synthase 1 P48651 Details

References:

  1. Kuge O, Nishijima M: Biosynthetic regulation and intracellular transport of phosphatidylserine in mammalian cells. J Biochem (Tokyo). 2003 Apr;133(4):397-403. Pubmed
  2. Kuge O, Hasegawa K, Ohsawa T, Saito K, Nishijima M: Purification and characterization of Chinese hamster phosphatidylserine synthase 2. J Biol Chem. 2003 Oct 24;278(43):42692-8. Epub 2003 Aug 11. Pubmed
  3. Ohsawa T, Nishijima M, Kuge O: Functional analysis of Chinese hamster phosphatidylserine synthase 1 through systematic alanine mutagenesis. Biochem J. 2004 Aug 1;381(Pt 3):853-9. Pubmed
  4. Steenbergen R, Nanowski TS, Nelson R, Young SG, Vance JE: Phospholipid homeostasis in phosphatidylserine synthase-2-deficient mice. Biochim Biophys Acta. 2006 Mar;1761(3):313-23. Epub 2006 Mar 31. Pubmed

9. Phosphatidylserine decarboxylase proenzyme

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Phosphatidylserine decarboxylase proenzyme Q9UG56 Details

References:

  1. Wu WI, Voelker DR: Reconstitution of phosphatidylserine transport from chemically defined donor membranes to phosphatidylserine decarboxylase 2 implicates specific lipid domains in the process. J Biol Chem. 2004 Feb 20;279(8):6635-42. Epub 2003 Dec 4. Pubmed
  2. Burgermeister M, Birner-Grunberger R, Heyn M, Daum G: Contribution of different biosynthetic pathways to species selectivity of aminoglycerophospholipids assembled into mitochondrial membranes of the yeast Saccharomyces cerevisiae. Biochim Biophys Acta. 2004 Nov 8;1686(1-2):148-60. Pubmed
  3. Burgermeister M, Birner-Grunberger R, Nebauer R, Daum G: Contribution of different pathways to the supply of phosphatidylethanolamine and phosphatidylcholine to mitochondrial membranes of the yeast Saccharomyces cerevisiae. Biochim Biophys Acta. 2004 Nov 8;1686(1-2):161-8. Pubmed
  4. Roggero R, Zufferey R, Minca M, Richier E, Calas M, Vial H, Ben Mamoun C: Unraveling the mode of action of the antimalarial choline analog G25 in Plasmodium falciparum and Saccharomyces cerevisiae. Antimicrob Agents Chemother. 2004 Aug;48(8):2816-24. Pubmed
  5. Voelker DR: Protein and lipid motifs regulate phosphatidylserine traffic in yeast. Biochem Soc Trans. 2005 Nov;33(Pt 5):1141-5. Pubmed

10. Scavenger receptor class B member 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Scavenger receptor class B member 1 Q8WTV0 Details

References:

  1. Yan X, Poelstra K, Scherphof GL, Kamps JA: A role for scavenger receptor B-I in selective transfer of rhodamine-PE from liposomes to cells. Biochem Biophys Res Commun. 2004 Dec 17;325(3):908-14. Pubmed
  2. Yancey PG, Kawashiri MA, Moore R, Glick JM, Williams DL, Connelly MA, Rader DJ, Rothblat GH: In vivo modulation of HDL phospholipid has opposing effects on SR-BI- and ABCA1-mediated cholesterol efflux. J Lipid Res. 2004 Feb;45(2):337-46. Epub 2003 Nov 1. Pubmed
  3. Nakagawa A, Shiratsuchi A, Tsuda K, Nakanishi Y: In vivo analysis of phagocytosis of apoptotic cells by testicular Sertoli cells. Mol Reprod Dev. 2005 Jun;71(2):166-77. Pubmed
  4. Zhang J, Fujii S, Wu Z, Hashioka S, Tanaka Y, Shiratsuchi A, Nakanishi Y, Nakanishi H: Involvement of COX-1 and up-regulated prostaglandin E synthases in phosphatidylserine liposome-induced prostaglandin E2 production by microglia. J Neuroimmunol. 2006 Mar;172(1-2):112-20. Epub 2005 Dec 20. Pubmed
  5. Osada Y, Shiratsuchi A, Nakanishi Y: Involvement of mitogen-activated protein kinases in class B scavenger receptor type I-induced phagocytosis of apoptotic cells. Exp Cell Res. 2006 Jun 10;312(10):1820-30. Epub 2006 Mar 10. Pubmed

Comments
comments powered by Disqus
Drug created on June 13, 2005 07:24 / Updated on September 24, 2013 11:58