Phosphatidylglycerol synthesis

L.R. Juneja, N. Hibi, T. Yamane, and S. Shimizu Repeated batch and continuous operations for phosphatidylglycerol synthesis from phosphatidylcholine with immobilized phospholipase U. Applied Microbiology and Biotechnology 27 (1987) 146-151. 

Sparace, SA and Mudd, JB (1982) Phosphatidylglycerol synthesis in spinach chloroplasts Characterization of the newly synthesized molecule. Plant Physiol ZQ. 1260 - 1264... 

Cytidine diphosphate 5 -l,2-diacylglycerol (periodate-oxidized) (19) Separation of membrane-bound enzymes involved in phosphatidylglycerol synthesis by affinity chromatography 152... 

E. coli and N. crassa are as active as lysyl-sRNA prepared from S. aureus. Unpublished studies (Gould and Lennarz, 1966) have recently shown that similar enzymatic activity for lysyl phosphatidylglycerol synthesis cannot be detected in particulate preparations in E. coli, Sarcina lutea, and M. lysodeikticus, but is present in Bacillus mega-terium and B. cereus. Moreover, Clostridium welchii, which earlier had been reported to contain both lysyl phosphatidylglycerol and alanyl phosphatidylglycerol (Macfarlane, 1962b) was found to form both of these lipids from lysyl-sRNA and alanyl-sRNA, respectively. 

Figure 1. Control of mitochondrial biogenesis by the nuclear genome. Most mitochondrial proteins, including cytochrome c, are nuclear gene products which are subsequently imported into mitochondria. Similarly, most enzymes involved in synthesis of mitochondrial phosphoplipids are encoded in the nuclear genome. Being located in the endoplasmatic reticulum, they synthesize phosphatidylcholine (PtdCho), phosphatidylserine (PtdSer), phosphatidylglycerol (PG) and phosphatidylinositol (Ptdins). The phospholipids are transferred to the outer membrane. The imported lipids then move into the inner membrane at contact sites. Mitochondria then diversify phospholipids. They decarboxylate phosphatidylserine to phosphatidylethanolamine (PtdEtN), but the main reaction is the conversion of imported phosphatidylglycerol to cardiolipin (CL). Cardiolipins localize mainly in the outer leaflet of the inner membrane.

In eukaryotes, phosphatidylglycerol, cardiolipin, and the phosphatidylinositols (all anionic phospholipids see Fig. 10-8) are synthesized by the same strategy used for phospholipid synthesis in bacteria. Phosphatidylglycerol is made exactly as in bacteria. Cardiolipin synthesis in eukaryotes differs slightly phosphatidylglycerol condenses with CDP-diacylglycerol (Fig. 21-26), not another molecule of phosphatidylglycerol as in E. coli (Fig. 21-25). 

Yeast pathways for the synthesis of phosphatidylserine, phosphatidylethanolamine, and phosphatidylglycerol are similar to those in bacteria phosphatidylcholine is formed by methylation of phosphatidylethanolamine. 

Figure 21-3 Major pathways of synthesis of fatty acids and glycerolipids in the green plant Arabidopsis. The major site of fatty acid synthesis is chloroplasts. Most is exported to the cytosol as oleic acid (18 1). After conversion to its coenzyme A derivative it is converted to phosphatidic acid (PA), diacylglycerol (DAG), and the phospholipids phosphatidylcholine (PC), phosphatidylinositol (PI), phosphatidylglycerol (PG), and phosphatidylethanolamine (PE). Desaturation also occurs, and some linoleic and linolenic acids are returned to the chloroplasts. See text also. From Sommerville and Browse.106 See also Figs. 21-4 and 21-5. Other abbreviations monogalactosyldiacylglycerol (MGD), digalactosyldiacylglycerol (DGD), sulfolipid (SL), glycerol 3-phosphate (G3P), lysophosphatidic acid (LPA), acyl carrier protein (ACP), cytidine diphosphate-DAG (CDP-DAG).

In E. coli, Phospholipid Synthesis Generates Phosphatidylethanolamine, Phosphatidylglycerol, and Diphosphatidylglycerol... 

Lipid synthesis is unique in that it is almost exclusively localized to the surface of membrane structures. The reason for this restriction is the amphipathic nature of the lipid molecules. Phospholipids are biosynthesized by acylation of either glycerol-3-phosphate or dihydroxyacetone phosphate to form phosphatidic acid. This central intermediate can be converted into phospholipids by two different pathways. In one of these, phosphatidic acid reacts with CTP to yield CDP-diacylglycerol, which in bacteria is converted to phosphatidylserine, phosphatidylglycerol, or diphos-... 

The isolation of mutants in S. typhimurium by Rick and Osborn (11,12) and mutants in E. coli by Nishijima and Raetz (44) that accumulate the Lipid A precursor indicate that KDO synthesis and Lipid A synthesis are not coordinately controlled. The initial steps in the synthesis of the Lipid A precursor are totally unknown. The temperature sensitive mutants of E. coli isolated by Nishijima and Raetz (44) that are defective in phosphaditylglyc-erol phosphate synthesis at 42°C and accumulate the Lipid A precursors indicate that there is some relationship between the synthesis of phosphatidylglycerol and LPS. The reasons for the acu-cumulation of the Lipid A precursors in this E. coli mutant are not obvious. We have shown that CDP-diglyceride, one of the substrates for phosphatidylglycerol phosphate synthesis, is an inhibitor of D-arabinose-5-phosphate isomerase with an 1 value... 

Joo, C. N. and Kates, M. (1969) Synthesis of the naturally occurring phytanyl diether analogs of phosphatidylglycerophosphate and phosphatidylglycerol, Biochim. Biophys. Acta 176, 278-297. 

Evidence for this model rests primarily on a correlation of lipid biosynthesis and translocation with protein synthesis and secretion. Increased synthesis of one causes increased synthesis of the other (Nesmayanova, 1982 Pag s, 1982). Both are inhibited by dissipation of the membrane potential (Bogdanov et al., 1984). Phosphatidylglycerol is present at the site of protein translocation, and may be involved in binding to the nascent chains and/or the ribosome (Bogdanov et al., 1985b). Bogdanov et al. (1985a) claim that secretion of alkaline phosphatase is accompanied by the appearance in freeze-fracture electron micro-... 

Subsequent phosphorylations catalyzed by specific kinases lead to the synthesis of pkosphatidylinositol 4,5-bisphosphate, the precursor of two intracellular messengers diacylglycerol and inositol l,4,S-trisphosphate (Section 14.2). If the alcohol is phosphatidylglycerol, the products are diphosphatidylglycerol (cardiolipin) and CMP. In eukaryotes, cardiolipin is located exclusively in inner mitochondrial membranes and plays an important role in the organization of the protein components of oxidative phosphorylation. 

FIGURE 21-26 Synthesis of cardiolipin and phosphatidylinositol in eukaryotes. These glycerophospholipids are synthesized using strategy 1 in Figure 21-24. Phosphatidylglycerol is synthesized as in bacteria (see Fig. 21-25). PI represents phosphatidylinositol. 

Fig. 6. Synthesis of phospholipid polar head groups. The three major phospholipid species in E. coli are synthesized by a total of six different enzymatic activities (1) phosphatidate cytidylyltransferase (Cds), (2) phosphatidylserine synthase (PssA), (3) phosphatidylserine decarboxylase (Psd), (4) phosphatidyl-glycerol phosphate synthase (PgsA), (5) phosphatidylglycerol phosphate phosphatase (PgpA or PgpB), and (6) cardiolipin synthase (els).

CTP phosphatidate cytidylyltransferase has been observed in plastids, mitochondria, and ER. In all three compartments, the CDP-diacylglycerol derived from phosphatidic acid is used in the synthesis of phosphatidylglycerol in mitochondria, the reaction of phosphatidylglycerol with a second CDP-diacylglycerol then produces cardiolipin. The ER can also incorporate CDP-diacylglycerol into phosphatidylinositol and phosphatidylserine. 

Free glycerol is also produced in synthesis of cardiolipin from phosphatidylglycerol (Figure 19.4)... 

The respiratory distress syndrome (RDS) of a premature infant such as Colleen Lakker is, in part, related to a deficiency in the synthesis of a substance known as lung surfactant. The major constituents of surfactant are dipalmitoylphosphatidyl-choline, phosphatidylglycerol, apoproteins (surfactant proteins Sp-A,B,C), and cholesterol. 

It is possible that some components of the lipoteichoic acid fraction are primers for the synthesis of wall teichoic acid, and are themselves constructed by rather different mechanisms from those above. There is evidence that phosphatidylglycerol in the cell membrane of Staphylococcus aureus can act as a precursor of glycerol in a form of lipoteichoic acid and that this can act as an acceptor for the construction of wall-type teichoic acid (Glaser and Lindsay, 1974). There is also good evidence to suggest that... 

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