Phosphatidylglycerol biosynthesis

Murata, N., Ishizaki, O. and Nishida, I. (1988) Chilling sensitivity and phosphatidylglycerol biosynthesis, in Plant Membranes structure, assembly and function (eds J.L. Harwood and T.J. Walton), The Biochemical Society, London, pp. 223-230. 

One enzyme present in the surfactant fluid is an acid phosphatase able to hydrolyze phosphatidylglycerol phosphate, perhaps functioning in the final step of biosynthesis of the phosphatidylglycerol present in the surfactant.6 Study of the action of the natural lung surfactant has led to development of artificial surfactant mixtures that are being used effectively to save many lives.d... 

The final reactions for the biosynthesis of phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol all occur on the cytosolic surface of the endoplasmic reticulum and Golgi apparatus (fig. 19.9). By contrast, phosphatidylglycerol and diphosphatidylglycerol are synthesized on the mitochondrial membrane where they remain for the most part. 

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-... 

Biosynthesis of phosphatidylinositols and phosphatidylglycerols. Enzymes (1) glycerol kinase (2) acyltransferases (3) phosphatidate cytidyltransferase (4) CDP-diacylglycerol inositol phosphatidate transferase (5) CDP-diacylglycerol in-glycerol-3-phosphate phosphatidate transferase (6) phosphatase (7) phosphatidylglycerol CDP-diacylglycerol phosphatidate transferase. 

A major fate of PA is conversion to DG that can be metabolized to PC, PE, and TG (Fig. 1). Alternatively, PA can react with CTP to form CDP-DG that is utilized for biosynthesis of the inositol phospholipids as well as phosphatidylglycerol (PG) and diphosphatidylglycerol (DPG) (Fig. 1). Inositol is a cyclohexane derivative in which all six carbons contain hydroxyl groups. The most common inositol isoform is myo-inositol but other less abundant inositols with different structures also occur. The first report of an inositol-containing lipid was in 1930 in Mycobacteria which is ironic since inositol lipids are rarely found in bacteria. Brain is the richest source of inositol-containing lipids, as first discovered by Folch and Wooley in 1942. In 1949, Folch described a PI phosphate (PI-P) that was later found to include PI and PI bisphosphate (PI-P2). The chemical structures of PI, PI-P, and PI-P2 were determined by Ballou and co-workers between 1959 and 1961. PI (1.7 pmol/g liver) constitutes -10% of the phospholipids in cells and tissues. PI-P and PI-P2 are present at much lower concentrations (1-3% of PI). In 1958, Agranoff and co-workers first reported the incorporation of [ HJinositol into PI. Subsequently, Paulus and Kennedy showed that CTP was the preferred nucleotide donor. 

See also Glycerophospholipid Pathway, Phosphatidylglycerol-3-Phosphate, Glycerophospholipid Biosynthesis in Bacteria, Glycerophospholipids, Glycerophospholipid Pathway,... 

Higashi, Y. Strominger, J.L. Biosynthesis of the peptidoglycan of bacterial cell walls. XX. Identification of phosphatidylglycerol and cardiolipin as cofactors for isoprenoid alcohol phosphokinase. J. Biol. Chem., 245, 3691-3696 (1970)... 

Whether the aoove reactions play any role in lipid biosynthesis is open to question. The naturally occurring phosphatidylglycerol is the optically active -T-j -glycerol enantiomer. Yang et al. (1967) found that the product of transphosphatidylation was a racemic mixture, although more recently Batrakov et al. (1975) found evidence for stereospecificity in the acyl transfer reaction with phospholipase D. 

Figure 5.1 Schematic iUuslTation of cardiolipin biosynthesis and remodeling pathways. Newly synthesized cardiolipin (CL) (immature or nascent CL) is formed by the condensation of phosphatidylglycerol (PG) and cytidine diphosphate-diacylglycerol (CDP-DAG) catalyzed by CL synthase. Immature CL is then deacylated to form monolysoCL and then reacylated using acyl chains from acyl CoA or Iransacylated from the sn-2 acyl chain of PC and PE species, leading to the formation of matured CL.

Recently the biosynthesis of the amino acyl derivative of phospha-tidylglycerol, lysyl phosphatidylglycerol (cf. Fig. 15), has been reported (Lennarz et al, 1966). Using C -lysine or C -lysyl-sRNA and crude extracts of S. aureus, the reaction was found to proceed in two steps. In the first step, catalyzed by a soluble enzyme, and requiring ATP, Mg++ and sRNA, lysine is activated to form lysyl-sRNA. A particulate enzyme catalyzes the second step of the reaction, the transfer of the lysyl moiety from sRNA to endogenous phosphatidylglycerol. This appears to be the first known instance in which amino acyl sRNA is involved in the synthesis of 0-acyl esters of amino acids. 

Figure 7.1 The biosynthesis of some important phospholipids. PtdChol = Phosphatidylcholine PtdEth = Phosphatidylethanolamine PtdSer = Phosphatidylserine PtdGly = Phosphatidylglycerol DiPtdGly = DIphosphatidylglycerol [cardiolipin) ...

---