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1,2-diacylphosphatidylethanolamine + L-serine
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the substrate is 6times better utilized than phosphatidylethanolamine plasmalogen
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L-1-phosphatidylcholine + L-serine
L-1-phosphatidylserine + choline
L-1-phosphatidylethanolamine + L-serine
L-1-phosphatidylserine + ethanolamine
phosphatidylethanolamine plasmalogen + L-serine
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additional information
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L-1-phosphatidylcholine + L-serine
L-1-phosphatidylserine + choline
isozyme PSS1
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r
L-1-phosphatidylcholine + L-serine
L-1-phosphatidylserine + choline
isozyme PSS1
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L-1-phosphatidylethanolamine + L-serine
L-1-phosphatidylserine + ethanolamine
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L-1-phosphatidylethanolamine + L-serine
L-1-phosphatidylserine + ethanolamine
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L-1-phosphatidylethanolamine + L-serine
L-1-phosphatidylserine + ethanolamine
isozyme PSS2
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L-1-phosphatidylethanolamine + L-serine
L-1-phosphatidylserine + ethanolamine
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L-1-phosphatidylethanolamine + L-serine
L-1-phosphatidylserine + ethanolamine
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L-1-phosphatidylethanolamine + L-serine
L-1-phosphatidylserine + ethanolamine
isozyme PSS2
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r
additional information
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no substrate: phosphatidylcholine
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additional information
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the enzyme synthesizes docosahexaenoic acid-phosphatidylserine much more efficiently than phosphatidylserine containing either 18:1 or 20:4 at the sn-2 position. Although no sn-1 fatty acyl preference is noted, phosphatidylserine synthase 2 exhibits significant preference toward docosahexaenoic acid compared with 18:1 or 20:4 at the sn-2 position
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additional information
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the enzyme synthesizes docosahexaenoic acid-phosphatidylserine much more efficiently than phosphatidylserine containing either 18:1 or 20:4 at the sn-2 position. Although no sn-1 fatty acyl preference is noted, phosphatidylserine synthase 2 exhibits significant preference toward docosahexaenoic acid compared with 18:1 or 20:4 at the sn-2 position
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additional information
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the enzyme synthesizes docosahexaenoic acid-phosphatidylserine much more efficiently than phosphatidylserine containing either 18:1 or 20:4 at the sn-2 position. Although no sn-1 fatty acyl preference is noted, phosphatidylserine synthase 2 exhibits significant preference toward docosahexaenoic acid compared with 18:1 or 20:4 at the sn-2 position
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additional information
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isozyme PSS1 shows a 2fold higher preference for sn-1 18:0 compared with 16:0 when the sn-2 position contains 18:1
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additional information
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isozyme PSS1 shows a 2fold higher preference for sn-1 18:0 compared with 16:0 when the sn-2 position contains 18:1
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additional information
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isozyme PSS1 shows a 2fold higher preference for sn-1 18:0 compared with 16:0 when the sn-2 position contains 18:1
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additional information
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the recombinant FLAG-tagged enzyme is also active with phosphatidylethanolamine plasmalogen, [C18(plasm),22:6-PS], which is six times less effective as a substrate than the corresponding ester-linked phosphatidylethanolamine species, the isozyme is active with oleic acid (OA; 18:1n-9), DHA (DHA; 22:6n-3), or arachidonic acid esters. Compounds analysis by mass spectroscopy. A carbonyl group next to the glycerol backbone in the substrate-binding pocket substantially increases the catalytic activity of PSS2. Isozyme PSS2 shows a 10fold preference for sn-1 18:0, when 22:6 is esterified at the sn-2 position. Synthesis of 18:0,22:6-PS is most efficient compared with 18:0,18:1-PS and with 18:0,20:4-PS. Substrate specificity and acyl chain preference of isozyme PS2, overview
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additional information
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the recombinant FLAG-tagged enzyme is also active with phosphatidylethanolamine plasmalogen, [C18(plasm),22:6-PS], which is six times less effective as a substrate than the corresponding ester-linked phosphatidylethanolamine species, the isozyme is active with oleic acid (OA; 18:1n-9), DHA (DHA; 22:6n-3), or arachidonic acid esters. Compounds analysis by mass spectroscopy. A carbonyl group next to the glycerol backbone in the substrate-binding pocket substantially increases the catalytic activity of PSS2. Isozyme PSS2 shows a 10fold preference for sn-1 18:0, when 22:6 is esterified at the sn-2 position. Synthesis of 18:0,22:6-PS is most efficient compared with 18:0,18:1-PS and with 18:0,20:4-PS. Substrate specificity and acyl chain preference of isozyme PS2, overview
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additional information
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the recombinant FLAG-tagged enzyme is also active with phosphatidylethanolamine plasmalogen, [C18(plasm),22:6-PS], which is six times less effective as a substrate than the corresponding ester-linked phosphatidylethanolamine species, the isozyme is active with oleic acid (OA; 18:1n-9), DHA (DHA; 22:6n-3), or arachidonic acid esters. Compounds analysis by mass spectroscopy. A carbonyl group next to the glycerol backbone in the substrate-binding pocket substantially increases the catalytic activity of PSS2. Isozyme PSS2 shows a 10fold preference for sn-1 18:0, when 22:6 is esterified at the sn-2 position. Synthesis of 18:0,22:6-PS is most efficient compared with 18:0,18:1-PS and with 18:0,20:4-PS. Substrate specificity and acyl chain preference of isozyme PS2, overview
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malfunction
gain-of-function mutation of PTDSS1 encoding phosphatidylserine synthase 1, a causative heterozygous missense mutations in gene PTDSS1, causes Lenz-Majewski syndrome (LMS), a syndrome of intellectual disability and multiple congenital anomalies that features generalized craniotubular hyperostosis. End-product inhibition of PSS1 by phosphatidylserine is markedly reduced in the mutant. The gain-of-function mutation is associated with regulatory dysfunction of PSS1. Phenotypes, overview
malfunction
mutation W277R of PTDSS1 encoding phosphatidylserine synthase 1 causes Lenz-Majewski hyperostotic dwarfism with hyperphosphoserinuria. Lenz-Majewski hyperostotic dwarfism (LMHD) is an ultra-rare Mendelian craniotubular dysostosis that causes skeletal dysmorphism and widely distributed osteosclerosis. In vivo, PTDSS1 defects cause LMHD and support enhanced biosynthesis of PTDS in the pathogenesis of LMHD, while in vitro, these PTDSS1 mutations are gain-of-function and increase PTDS production. Phenotype, overview
metabolism
link between phosphatidylserine synthesis and bone metabolism
metabolism
phosphatidylserine is synthesized in mammalian cells by two integral membrane proteins, PS synthase 1 and 2 (PSS1 and PSS2). These enzymes catalyze the formation of phosphatidylserine by an exchange reaction in which serine replaces the head group of the corresponding substrate phospholipids, phosphatidylcholine (PC) for isozyme PSS1 and phosphatidylethanolamine (PE) for isozyme PSS2
physiological function
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docosahexaenoic acid positively modulates phosphatidylserine biosynthesis. Over-expression of PSS2 alters neither the phosphatidylserine level nor the effect of docosahexaenoic acid on phosphatidylserine increase
physiological function
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docosahexaenoic acid positively modulates phosphatidylserine biosynthesis. Over-expression of PSS2 alters neither the phosphatidylserine level nor the effect of docosahexaenoic acid on phosphatidylserine increase
physiological function
docosahexaenoic acid positively modulates phosphatidylserine biosynthesis. Over-expression of PSS2 alters neither the phosphatidylserine level nor the effect of docosahexaenoic acid on phosphatidylserine increase
physiological function
expression of PSS2 in ethanolamine-requiring mutant Chinese hamster ovary cells defective in PSS1, reverses the ethanolamine auxotrophy. However, the phosphatidylethanolamine content is not normalized unless the culture medium is supplemented with ethanolamine. In both mutant chinese hamster ovary cells and hepatoma cells transfected with PSS2 cDNA the rate of synthesis of phosphatidylserine and phosphatidylserine-derived phosphatidylethanolamine does not exceed that in parental chinese hamster ovary cells or control McArdle cells, respectively. Expression of murine PSS2 in McArdle cells does not inhibit phosphatidylethanolamine synthesis via the CDP-ethanolamine pathway, whereas expression of similar levels of PSS1 activity inhibit this pathway by approx. 50%
physiological function
induced apoptosis with staurosporine in four Chinese hamster ovary cell lines that are deficient in PSS1, EC 2.7.8.8, and/or PSS2. In all cell lines, regardless of their content of PSS1 and/or PSS2, apoptosis occurrs to approximately the same extent, and within approximately the same time frame, as in parental CHO-K1 cells. Cells that are deficient in either PSS1 or PSS2, as well as cells that are deficient in both PSS1 and PSS2, externalize normal amounts of phosphatidylserine
physiological function
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intercrosses of mice lacking PSS1, EC 2.7.8.8, and PSS2-/- mice yield mice with three disrupted Pss alleles but no double knockout mice. In PSS1-/-PSS2+/- and PSS1+/-PSS2-/- mice, serine exchange activity is reduced by 65-91%,and the tissue content of phosphatidylserine and phosphatidylethanolamine is also decreased. Elimination of either PSS1 or PSS2, but not both, is compatible with mouse viability, mice can tolerate as little as 10% of normal total serine-exchange activity, and mice survive with significantly reduced phosphatidylserine and phosphatidylethanolamine content
physiological function
introduction of the pssB cDNA into CHO-K1 cells results in striking increases in both the serine and ethanolamine base exchange activities. The pssB cDNA is incapable of increasing the choline base exchange activity. The expression of the pssB gene in Sf9 insect cells also results in striking increases in both serine and ethanolamine base exchange activities. The pssB cDNA transforms a phosphatidylserine-auxotrophic mutant of CHO-K1 cells lacking PSS I, EC 2.7.8.8, to phosphatidylserine prototrophy. The phosphatidylserine content of the resultant transformant grown without exogenous phosphatidylserine for 2 days is 4-fold that of the mutant and similar to that of CHO-K1 cells, indicating that the pssB cDNA complements the phosphatidylserine biosynthetic defect of the PSS I-lacking mutant
physiological function
mutant defective in PSS II show 5% of the activity in the homogenate CHO-K1 cells and 10% of the activity in the homogenate of cells lacking PSS I, EC 2.7.8.8. The PSS II mutant grows well in medium supplemented with phosphatidylserine. However, in the medium supplemented with phosphatidylethanolamine, the PSS II-mutant is incapable of growth. In the medium with exogenous phosphatidylethanolamine, the PSS II-mutant is defective in phosphatidylserine biosynthesis
physiological function
phosphatidylserine biosynthesis in Chinese hamster ovary cells increases 2.5fold during UV-induced apoptosis and is not reversed by caspase inhibitor, Z-VAD-FMK, i.e. benzyloxycarbonyl-Val-Ala-DL-Asp-fluoromethylketone. Stimulation of synthesis is less specific for phosphatidylserine as similar levels of stimulation are observed for sphingomyelin biosynthesis. PSS I- , EC 2.7.8.8, or PSS II-expressing cells have higher basal levels of phosphatidylserine biosynthesis compared with vector control cells. When cells are exposed to UV light to induce apoptosis, phosphatidylserine biosynthesis is further stimulated 1.5- and 2fold in PSS I- and PSS II-expressing cells respectively. Cells overexpressing PSS I and II are actually resistant to UV-induced apoptosis
physiological function
PSS II activity is inhibited by exogenous phosphatidylserine and overproduction of PSS II leads to the loss of normal control of PSS II activity by exogenous phosphatidylserine. PSS II-overproducing cells cultivated without exogenous phosphatidylserine exhibit a normal phosphatidylserine biosynthetic rate similar to that in CHO-K1 cells. Stable transformation of R97K mutant PSS II, leads to a 4fold higher phosphatidylserine biosynthetic rate
physiological function
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the ability of testis extracts from PSS2-deficient mice to catalyze serine exchange is reduced by more than 95%, reductions of 90% are found in the brain and liver. There are no perturbations in the phospholipid content of any of these tissues. The expression of PSS1, EC 2.7.8.8, is not upregulated in Pss2-deficient cells and tissues. Testis weight is reduced in Pss2-deficient mice, and some of the male mice are infertile
physiological function
the enzyme plays a key role in phosphatidylserine accumulation in brain and testis through high activity toward docosahexaenoic acid-containing substrates
physiological function
isozyme PSS1 is one of two enzymes involved in the production of phosphatidylserine
physiological function
isozyme PSS1 promotes the biosynthesis of phosphatidylserine (PTDS), which is a functional constituent of lipid bilayers. PTDS binds calcium within matrix vesicles to engender hydroxyapatite crystal formation, and may enhance mesenchymal stem cell differentiation leading to osteogenesis
physiological function
isozyme PSS2 may play a key role in phosphatidylserine accumulation in brain and testis through high activity toward DHA-containing substrates that are abundant in these tissues
physiological function
expression of PSS2 is necessary for normal growth of procyclic trypanosomes and PSS2 represents the unique route for phosphatidylserine formation in Trypanosoma brucei. Downregulation of TbPSS2 by RNAi for 3 days inhibits incorporation of serine into newly synthesized phosphatidylserine by 94.8
physiological function
PSS regulates cell growth, lipid storage and mitochondrial function. RNAi-induced decreased of expression reduces phosphatidylserine and depletes plasma membrane Akt. Loss of PSS by RNAi reduces cell size and causes ectopic lipid storage in Drosophila salivary gland. Overexpressing phosphatidylserine decarboxylase enhances the cell growth defect and suppresses the ectopic lipid storage phenotype of pss knockdown. The reduction of mitochondrial phosphatidylserine impairs mitochondrial protein import and mitochondrial integrity
physiological function
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expression of PSS2 is necessary for normal growth of procyclic trypanosomes and PSS2 represents the unique route for phosphatidylserine formation in Trypanosoma brucei. Downregulation of TbPSS2 by RNAi for 3 days inhibits incorporation of serine into newly synthesized phosphatidylserine by 94.8
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Yu, A.; McMaster, C.R.; Byers, D.M.; Ridgway, N.D.; Cook, H.W.
Resistance to UV-induced apoptosis in Chinese-hamster ovary cells overexpressing phosphatidylserine synthases
Biochem. J.
381
609-618
2004
Cricetulus griseus (O08888)
brenda
Grandmaison, P.A.; Nanowski, T.S.; Vance, J.E.
Externalization of phosphatidylserine during apoptosis does not specifically require either isoform of phosphatidylserine synthase
Biochim. Biophys. Acta
1636
1-11
2004
Cricetulus griseus (O08888)
brenda
Wen, Z.; Kim, H.Y.
Inhibition of phosphatidylserine biosynthesis in developing rat brain by maternal exposure to ethanol
J. Neurosci. Res.
85
1568-1578
2007
Rattus norvegicus
brenda
Arikketh, D.; Nelson, R.; Vance, J.E.
Defining the importance of phosphatidylserine synthase-1 (PSS1): unexpected viability of PSS1-deficient mice
J. Biol. Chem.
283
12888-12897
2008
Mus musculus
brenda
Guo, M.; Stockert, L.; Akbar, M.; Kim, H.Y.
Neuronal specific increase of phosphatidylserine by docosahexaenoic acid
J. Mol. Neurosci.
33
67-73
2007
Homo sapiens, Mus musculus, Cricetulus griseus (O08888)
brenda
Stone, S.J.; Vance, J.E.
Cloning and expression of murine liver phosphatidylserine synthase (PSS)-2: differential regulation of phospholipid metabolism by PSS1 and PSS2
Biochem. J.
342
57-64
1999
Mus musculus (Q9Z1X2)
brenda
Tomohiro, S.; Kawaguti, A.; Kawabe, Y.; Kitada, S.; Kuge, O.
Purification and characterization of human phosphatidylserine synthases 1 and 2
Biochem. J.
418
421-429
2009
Homo sapiens (Q9BVG9)
brenda
Kuge, O.; Saito, K.; Nishijima, M.
Cloning of a Chinese hamster ovary (CHO) cDNA encoding phosphatidylserine synthase (PSS) II, overexpression of which suppresses the phosphatidylserine biosynthetic defect of a PSS I-lacking mutant of CHO-K1 cells
J. Biol. Chem.
272
19133-19139
1997
Cricetulus griseus (O08888)
brenda
Saito, K.; Nishijima, M.; Kuge, O.
Genetic evidence that phosphatidylserine synthase II catalyzes the conversion of phosphatidylethanolamine to phosphatidylserine in Chinese hamster ovary cells
J. Biol. Chem.
273
17199-17205
1998
Cricetulus griseus (O08888)
brenda
Kuge, O.; Saito, K.; Nishijima, M.
Control of phosphatidylserine synthase II activity in Chinese hamster ovary cells
J. Biol. Chem.
274
23844-23849
1999
Cricetulus griseus (O08888)
brenda
Stone, S.J.; Vance, J.E.
Phosphatidylserine synthase-1 and -2 are localized to mitochondria-associated membranes
J. Biol. Chem.
275
34534-34540
2000
Rattus norvegicus, Cricetulus griseus (O08888)
brenda
Bergo, M.O.; Gavino, B.J.; Steenbergen, R.; Sturbois, B.; Parlow, A.F.; Sanan, D.A.; Skarnes, W.C.; Vance, J.E.; Young, S.G.
Defining the importance of phosphatidylserine synthase 2 in mice
J. Biol. Chem.
277
47701-47708
2002
Mus musculus
brenda
Kuge, O.; Hasegawa, K.; Ohsawa, T.; Saito, K.; Nishijima, M.
Purification and characterization of Chinese hamster phosphatidylserine synthase 2
J. Biol. Chem.
278
42692-42698
2003
Cricetulus griseus (O08888), Cricetulus griseus
brenda
Kimura, A.K.; Kim, H.Y.
Phosphatidylserine synthase 2: high efficiency for synthesizing phosphatidylserine containing docosahexaenoic acid
J. Lipid Res.
54
214-222
2013
Mus musculus, Mus musculus (Q99LH2), Mus musculus (Q9Z1X2)
brenda
Whyte, M.P.; Blythe, A.; McAlister, W.H.; Nenninger, A.R.; Bijanki, V.N.; Mumm, S.
Lenz-Majewski hyperostotic dwarfism with hyperphosphoserinuria from a novel mutation in PTDSS1 encoding phosphatidylserine synthase 1
J. Bone Miner. Res.
30
606-614
2015
Homo sapiens (P48651), Homo sapiens
brenda
Sousa, S.B.; Jenkins, D.; Chanudet, E.; Tasseva, G.; Ishida, M.; Anderson, G.; Docker, J.; Ryten, M.; Sa, J.; Saraiva, J.M.; Barnicoat, A.; Scott, R.; Calder, A.; Wattanasirichaigoon, D.; Chrzanowska, K.; Simandlova, M.; Van Maldergem, L.; Stanier, P.; Beales, P.L.; Vance, J.E.; Moore, G.E.
Gain-of-function mutations in the phosphatidylserine synthase 1 (PTDSS1) gene cause Lenz-Majewski syndrome
Nat. Genet.
46
70-76
2014
Homo sapiens (P48651), Homo sapiens (Q9BVG9), Homo sapiens
brenda
Farine, L.; Jelk, J.; Choi, J.Y.; Voelker, D.R.; Nunes, J.; Smith, T.K.; Buetikofer, P.
Phosphatidylserine synthase 2 and phosphatidylserine decarboxylase are essential for aminophospholipid synthesis in Trypanosoma brucei
Mol. Microbiol.
104
412-427
2017
Trypanosoma brucei (Q57WJ1), Trypanosoma brucei, Trypanosoma brucei 927/4 (Q57WJ1)
brenda
Yang, X.; Liang, J.; Ding, L.; Li, X.; Lam, S.M.; Shui, G.; Ding, M.; Huang, X.
Phosphatidylserine synthase regulates cellular homeostasis through distinct metabolic mechanisms
PLoS Genet.
15
e1008548
2019
Drosophila melanogaster (Q9VPD3)
brenda