Phosphatidate, phosphatidic acid turnover

Phospholipid turnover also takes place in an asymmetric manner. The enzymes responsible for phospholipid turnover in response to receptor-mediated phospholipase c activation are active from the cytoplasmic surface of the membrane. Likewise, diacylglycerol kinases converting the product of phospholipase c back into the key intermediate of phospholipid biosynthesis, phosphatidic acid, are also located on the cytoplasmic smface of the membrane (Sanjuan et al., 2001). 

Munnik, T., Van Himbergen, J.A.J., Ter Riet, B., Braun, F.-J., Irvine, F.F., Van den Ende, H. and Musgrave, A., 1998b, Detailed analysis of the turnover of polyphosphoinositides and phosphatidic acid upon activation of phospholipases C and D in Chlamydomonas cells treated with non-permeabilizing concentrations of mastoparan. Planta 207 133-145. 

Fig. 9. Phospholipid turnover. The 1,2-diacylglyceroI kinase cycle involves the (1) transfer of the sn-1 -glycerol phosphate moiety from phosphatidylglycerol to MDO by the enzyme MdoB. (2) Diacylglycerol kinase converts the diacylglycerol to phosphatidic acid, which can regenerate the phosphatidylglycerol (see Fig. 6). Phosphatidylethanolamine cycling involves (3) the transfer of an acyl chain to membrane lipoprotein and (4) re-esterification of the 1-position by 2-acylgiycerophosphoethanolamine (Aas).

Raymond, V., Leung, P.C.K. and Labrie, F. (1983). Stimulation of PGp2a of phosphatidic acid-phosphatidylinositol turnover in rat luteal cells. Biochem. Biophys. Res. Commm., 116, 39-46... 

The hydrolysis of phosphatidylinositol may be of special biological interest [32,33]. This phospholipid consists largely of l-stearoyl-2-arachidonoyl-glycero-3-phosphoinositol in many tissues (e.g. platelets, brain, liver and mouse pancreas [34,35]). Stimulation of several endocrine or exocrine glands has been found to involve an increased turnover of this phospholipid and formation of phosphatidic acid (see ref. 33 for review). This phosphatidylinositol response might be important for hormone induced mobilization of Ca ", at least in some tissues (see refs. 33, 36, 37 and for critical comments refs. 38 and 39). 

Stimulation of P 2 Turnover in Phosphoinositide and Phosphatidic Acid of Tissue Slices... 

Wilson and Rinne (1976) have supplied soybean cotyledons with labeled acetate and labeled glycerol. Phosphatidic acid and DG turned over rapidly, as might be expected (half-times of 6 min). Half-times of 30-60 min were calculated for PC, PE, and Pi, but inspection of the data shows relatively little change in specific activity after 60 min. Moore (1977) examined phospholipid turnover in soybean suspension cultures and found much longer half-times than Wilson and Rinne (1976). Phosphatidylcholine labeled with choline had a half-life of 36 h, and PE labeled with ethanolamine decayed in three phases with half-lives of 12, 34, and 136 h. 

Fig. 1. Stimulus-induced turnover of phosphatidylinositol 4,5-bisphosphate (PIPo) and the role of turnover products in signal transduction. PI, phosphatidylinositol PIP, phosphatidylinositol 4-phosphate PIPo, phosphatidylinositol 4,5 bisphosphate IP, inositol trisphosphate IP, inositol tetrakisphosphate IPo inositol bisphosphate IP, inositol monophosphate ER, endoplasmic reticulum DG, diacylglycerol MG, monoglyceride AA, arachidonic acid PA, phosphatidic acid. [Adapted from 38]...

Formation and turnover of stearoyl,arachidonoyl phosphatidic acid... 

The I PI-phosphatidic acid formed in the stimulated state in pancreas is lost from the phosphatidic acid fraction, together with the specific disappearance of (18 0,20 4)phosphatidic acid. This indicates that the (18 0,20 4)phosphatidic acid which is formed from phosphatidylinositol in the stimulated state is the only species of phosphatidic acid which undergoes increased turnover of its phosphate group. 

To summarize these changes which I have discussed, stimulation of salt gland and pancreas with acetylcholine leads to a breakdown of phosphatidylinositol. Under some conditions, the (18 0,20 4)-diglyceride moiety of this phosphatidylinositol is converted almost quantitatively to (18 0,20 4)phosphatidic acid. During the stimulated state, this novel species of phosphatidic acid undergoes continuous turnover of its phosphate group, presumably with (18 0, 20 4)diglyceride as an intermediate. It is specifically used for the resynthesis of phosphatidylinositol when stimulated tissue reverts to the unstimulated state (Fig. 1). 

The hormone pancreozymin (cholecystokinin-pancreoz3miin) stimulates the protein secretory cycle in the exocrine pancreas (Harper Raper, 1943) it also elicits phosphatidylinositol breakdown, formation of phosphatidic acid, and increased turnover of the polar headgroups of these phosphatides. These effects are essentially the same as those observed in response to acetylcholine (Hokin, M.R.,... 

The fact that phosphatide fatty acids of different tissues can be replaced only partly by elaidic acid alone restricts the applicability of elaidic acid as indicator. Not more than 30% of phosphatide fatty acids of liver and of small intestine can be replaced by elaidic acid, and not more than 7% of those of brain and still less in testes can thus be replaced. Furthermore, in order to obtain quantitative results from experiments carried out with elaidic acid as indicator, we should know, beside the elaidic acid content of the phosphatides, the elaidic acid content of the fatty acid mixture available for phosphatide synthesis in cells of the organ. Lack of knowledge of the concentration of the tracer in the precursor of the compound whose rate of formation we wish to determine is the greatest obstacle in the application of isotopic and nonisotopic indicators to determination of turnover rate. 

In earlier investigations of turnover of nucleic acid, acid-soluble and phosphatide components of tissue were extracted with trichloroacetic acid and with ethei -alcohol, and the activity of the residual part was determined. Such residues contain, beside thymonucleic apid, ribonucleic acid and possibly also phosphoproteins. Since the rate of renewal of ribonucleic acid is much larger than that of thymonucleic acid, no conclusion about the value for thymonucleic acid can be drawn from these experiments. 

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