Disease relevance of Ptdss1

• Mouse liver PtdSer synthase-1 was also expressed in McArdle 7777 rat hepatoma cells [1].

High impact information on Ptdss1

• As judged by Northern blots, the expression of Pss1 was not up-regulated in Pss2-deficient cells and tissues [2].
• In mammalian cells, phosphatidylserine is synthesized by two different enzymes, phosphatidylserine synthase (PSS)-1 and -2, via a base exchange reaction in which the head group of a phospholipid (phosphatidylcholine or phosphatidylethanolamine) is replaced by l-serine [3].
• The mRNA encoding PSS1 was most abundant in kidney, brain, and liver, whereas PSS2 mRNA was most highly expressed in testis [3].
• Since the amino acid sequences of PSS1 and PSS2 are only approximately 30% identical, it is likely that they are encoded by different genes [3].
• The transcriptional initiation site for PSS1 was identified 111 base pairs upstream of the ATG specifying the start of translation [3].

Chemical compound and disease context of Ptdss1

• Cloning and expression of mouse liver phosphatidylserine synthase-1 cDNA. Overexpression in rat hepatoma cells inhibits the CDP-ethanolamine pathway for phosphatidylethanolamine biosynthesis [1].
• In both M.9.1.1 and hepatoma cells transfected with PSS2 cDNA the rate of synthesis of PtdSer and PtdSer-derived PtdEtn did not exceed that in parental CHO cells or control McArdle cells respectively, in contrast to cells expressing similar levels of murine PSS1 [4].

Biological context of Ptdss1

• Whether Pss1 and Pss2 are both required for mammalian growth and development is not known, and no data exist on the relative contributions of the two enzymes to serine exchange activities in different tissues [2].
• We have screened a murine liver genomic DNA library, included in bacterial artificial chromosomes, with full-length murine PSS1 cDNA and isolated a clone containing the majority of the PSS1 gene [3].

Anatomical context of Ptdss1

• Phosphatidylserine synthase-1 and -2 are localized to mitochondria-associated membranes [5].
• The deduced protein sequence is >90% identical to that of PtdSer synthase-1 from Chinese hamster ovary cells and a sequence from a human myeloblast cell line [1].
• We have now cloned and stably expressed a murine PSS2 cDNA in McArdle cells and M.9.1.1 cells [which are ethanolamine-requiring mutant Chinese hamster ovary (CHO) cells defective in PSS1] [4].
• The concerted synthesis of phospholipids derived from serine involving two microsomal enzymes (phosphatidylserine synthase and phosphatidylethanolamine N-methyltransferase) and a mitochondrial one (phosphatidylserine decarboxylase) occurs in reconstituted cell-free systems [6].

Associations of Ptdss1 with chemical compounds

• In general agreement with the levels of mRNA expression, the choline exchange activity (contributed by PSS1, but not PSS2) was highest in brain, whereas serine and ethanolamine exchange activities were highest in testis and kidney [3].
• Phosphatidylserine (PtdSer) is synthesized in mammalian cells by two base-exchange enzymes: PtdSer synthase (PSS)-1 primarily uses phosphatidylcholine as a substrate for exchange with serine, whereas PSS2 uses phosphatidylethanolamine (PtdEtn) [4].
• The activity of PSS1 in vitro and the synthesis of PtdSer and PtdSer-derived PtdEtn were increased, whereas PtdEtn synthesis from the CDP-ethanolamine pathway was inhibited [Stone, Cui and Vance (1998) J. Biol. Chem. 273, 7293-7302] [4].

Analytical, diagnostic and therapeutic context of Ptdss1

• According to reverse transcriptase-mediated polymerase chain reaction, PSS1 and PSS2 mRNAs were expressed in all murine tissues examined [3].
• According to immunoblotting of proteins from both CHO-K1 cells and murine liver, PSS1 is localized to MAM, and in hepatoma cells stably expressing PSS1 this protein is highly enriched in MAM [5].

References