Metabolism and Functions of Phosphatidylserine in Mammalian Brain

Mozzi, Rita; Buratta, Sandra; Goracci, G

doi:10.1023/a:1022412831330

Cited by 82 publications

(75 citation statements)

References 162 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PTDSS1 expression was highest in almost all areas of the brain and throughout fetal and postnatal life, with peak expression occurring during mid-gestation. Consistent with these observations, phosphatidylserine is important for brain function and development, and levels of phosphatidylserine and phosphatidylethanolamine are particularly high in mammalian brains 16 . Indeed, dietary supplementation with phosphatidylserine is widely, albeit controversially, used for improving memory, cognitive function and exercise performance 32,33 .…”

supporting

confidence: 56%

“…Phosphatidylserine represents 3-10% of all membrane phospholipids in mammalian tissues and cultured cells 14 . The relatively low abundance of phosphatidylserine is outweighed by its physiological importance, attributable to its unique physical and biochemical properties 15 and its specific tissue 13,16 and subcellular distributions 13,17 . Functions of phosphatidylserine at the cell surface, including roles in apoptosis, coagulation and the internalization of viruses, have been studied extensively, but phosphatidylserine also participates in intracellular processes by interacting with key signaling proteins such as the Ras and Rho family of GTPases and protein kinase C 13 .…”

mentioning

confidence: 99%

See 1 more Smart Citation

Gain-of-function mutations in the phosphatidylserine synthase 1 (PTDSS1) gene cause Lenz-Majewski syndrome

Jenkins²,

et al. 2013

View full text Add to dashboard Cite

Lenz-Majewski syndrome (LMS) is a syndrome of intellectual disability and multiple congenital anomalies that features generalized craniotubular hyperostosis. By using whole-exome sequencing and selecting variants consistent with the predicted dominant de novo etiology of LMS, we identified causative heterozygous missense mutations in PTDSS1, which encodes phosphatidylserine synthase (PSS ). PSS is one of two enzymes involved in the production of phosphatidylserine. Phosphatidylserine synthesis was increased in intact fibroblasts from affected individuals, and end-product inhibition of PSS by phosphatidylserine was markedly reduced. Therefore, these mutations cause a gain-of-function effect associated with regulatory dysfunction of PSS . We have identified LMS as the first human disease, to our knowledge, caused by disrupted phosphatidylserine metabolism. Our results point to an unexplored link between phosphatidylserine synthesis and bone metabolism.

show abstract

supporting

confidence: 56%

mentioning

confidence: 99%

Gain-of-function mutations in the phosphatidylserine synthase 1 (PTDSS1) gene cause Lenz-Majewski syndrome

Jenkins²,

et al. 2013

View full text Add to dashboard Cite

show abstract

“…In human gray matter, 22:6n-3 accounts for .36% of the fatty acyl species of PS (5-7). Because 22:6n-3 appears to be essential for the normal development and functioning of the nervous system (6,(8)(9)(10)(11), it is likely that PS plays an important role in the nervous system and in vision (reviewed in Ref. 4).…”

mentioning

confidence: 99%

Thematic Review Series: Glycerolipids. Phosphatidylserine and phosphatidylethanolamine in mammalian cells: two metabolically related aminophospholipids

Vance

2008

Journal of Lipid Research

427

355

View full text Add to dashboard Cite

Phosphatidylserine(PS)andphosphatidylethanolamine (PE) are two aminophospholipids whose metabolism is interrelated. Both phospholipids are components of mammalian cell membranes and play important roles in biological processes such as apoptosis and cell signaling. PS is synthesized in mammalian cells by base-exchange reactions in which polar head groups of preexisting phospholipids are replaced by serine. PS synthase activity resides primarily on mitochondria-associated membranes and is encoded by two distinct genes. Studies in mice in which each gene has been individually disrupted are beginning to elucidate the importance of these two synthases for biological functions in intact animals. PE is made in mammalian cells by two completely independent major pathways. In one pathway, PS is converted into PE by the mitochondrial enzyme PS decarboxylase. In addition, PE is made via the CDP-ethanolamine pathway, in which the final reaction occurs on the endoplasmic reticulum and nuclear envelope. The relative importance of these two pathways of PE synthesis has been investigated in knockout mice. Elimination of either pathway is embryonically lethal, despite the normal activity of the other pathway. PE can also be generated from a base-exchange reaction and by the acylation of lyso-PE. Cellular levels of PS and PE are tightly regulated by the implementation of multiple compensatory mechanisms.-Vance, J. E. Phosphatidylserine and phosphatidylethanolamine in mammalian cells: two metabolically related aminophospholipids.

show abstract

“…The membrane phospholipids phosphatidic acid (PA) and phosphatidylserine (PS) are essential to cellular functioning, acting as a biological detergent, keeping fatty substances soluble and cell membranes flexible [1,2]. During the pathogenesis of several age-related neurodegenerative diseases, including Alzheimer's disease, the neuronal membrane lipid composition is altered in the brain [3,4].…”

Section: Phosphatidylserine (Ps) and Phosphatidic Acid (Pa) In Memorymentioning

confidence: 99%

Soy Lecithin-Derived Phosphatidylserine Plus Phosphatidic Acid: Effects on Brain Functions in Elderly Patients with Alzheimer's Disease and Dementia

Moré¹,

Rutenberg²

2017

J Aging Sci

View full text Add to dashboard Cite

Phosphatidic acid (PA) and phosphatidylserine (PS) and are natural constituents of healthy brain cell membranes, which have been recognized since the 1970s as essential to normal neuronal functioning. PA is a precursor in the formation of other phospholipids, including PS and phosphatidylethanolamine (PE). Also, it has an impact on membrane rigidity/flexibility, which is important in modulating exo-and endocytosis. PS is also an important precursor for PE synthesis. Since PS predominantly occurs in brain cells, but normal diets do not include the consumption of brains, PS is available to our brains mostly via natural "production" in our bodies.Here, we present a tabulated literature survey of clinical studies on PS and/or PA regarding brain function in elderly people. In addition we give a summary on two of our our already published pilot studies performed with a brain-health food supplement containing a proprietary blend of 100 mg PS and 80 mg PA produced from soy lecithin: A three-month double-blind, placebo-controlled study demonstrated the positive influence of three PS+PA capsules/ day, (300 mg PS+240 mg PA per day; n=40)) or placebo (n=32) on memory and mood in functioning, non-depressive elderly people with memory problems. In a two-month randomized, double-blind, placebo-controlled study, three PS+PA capsules/day (300 mg PS+240 mg PA per day; n=56) or placebo (n=40) improved daily functioning, mental health, emotional state, and self-reported general condition in patients with Alzheimer's disease (AD).Altogether there is encouraging clinical data that PS+PA supplementation could be beneficial to AD patients and other elderly people with memory or cognition problems. Long-term studies are, however, still lacking. Keywords: Phosphatidylserine (PS) and Phosphatidic Acid (PA) in MemoryThe membrane phospholipids phosphatidic acid (PA) and phosphatidylserine (PS) are essential to cellular functioning, acting as a biological detergent, keeping fatty substances soluble and cell membranes flexible [1,2]. During the pathogenesis of several age-related neurodegenerative diseases, including Alzheimer's disease, the neuronal membrane lipid composition is altered in the brain [3,4]. Also, the lipid raft composition appears to be altered in neurodegenerative diseases [5]. PS (and PA), produced by enzymatic conversion of soybean lecithin, avoids possible regulatory and safety issues regarding bovine spongiform encephalopathy. Soy lecithin-derived PS is absorbed and metabolized, with elevated serum levels for at least 1.5 hours after an oral dose, as has been shown within a kinetic study on 8 human volunteers. The baseline serum level of PS in relation to the level of total serum phospholipids was around 2%. 30 minutes after ingestion, it started to increase, peaking at 90 minutes after intake at around 4%, and returning to the basal level 180 minutes after intake [23].Recently, oral administration of phosphatidylcholine/phosphatidylethanolamine (PE) -transphosphatidylated PS has been shown to improve memory imp...

show abstract

Metabolism and Functions of Phosphatidylserine in Mammalian Brain

Cited by 82 publications

References 162 publications

Gain-of-function mutations in the phosphatidylserine synthase 1 (PTDSS1) gene cause Lenz-Majewski syndrome

Gain-of-function mutations in the phosphatidylserine synthase 1 (PTDSS1) gene cause Lenz-Majewski syndrome

Thematic Review Series: Glycerolipids. Phosphatidylserine and phosphatidylethanolamine in mammalian cells: two metabolically related aminophospholipids

Soy Lecithin-Derived Phosphatidylserine Plus Phosphatidic Acid: Effects on Brain Functions in Elderly Patients with Alzheimer's Disease and Dementia

Contact Info

Product

Resources

About