Phosphatidal derivative

Another group of phosphatides contain the hexahydroxycyclohexane known as inositol (Fig. 8-2, see also Chapter 21).16 Phosphatidylinositol, as well as smaller amounts of phosphatides derived from phosphate esters of inositol are present in membranes... 

Compounds 19 and 20 along with some acylated phosphatidic derivatives in addition to 1,2-dioleoylphosphatidic acid, were tested using the particle bioassay [83]. Commercially available l-oleoyl-2-lysophosphatidic acid (21) possessed repellent activity which was enhanced by monomethylation. When A. cochlioides zoospores were pre-treated with an excess of the natural stimulant N-frans-feruloyltyramine (19), and then exposed to Chromosorb W AW particles coated with various test compounds, it was found that 1 -oleoyl-2-lysophosphatidic (21, 100 ppm) and its monomethyl ester (22) (10 ppm), as well as the natural repellent 1-linoleoyl-2-lysophosphatidic acid monomethyl ester (20, 30 ppm), effectively inhibited zoospore motility [83], However, l-oleoyl-2-lysophosphatidic acid dimethyl ester (23) and 1,2-dioleoylphosphatidic acid tested with and without the stimulant (19) showed neither repellent nor motility inhibitory activity. The bioassay revealed that compounds possessing repellent activity are monoacylated phosphatidic acid derivatives containing at least one hydroxy group on the phosphoryl unit [83]. 

Animal and human organs contain ether-ester-, alkenyl ether-ester-and diester phosphatides, derived from ethanolamine or choline diether-and dialkenyl ether phosphatides may occur in smaller amounts. 

Phosphatidic acids not only are intennediates in the biosynthesis of triacylglycerols but also are biosynthetic precursors of other members of a group of compounds called phosphoglycerides or glycerol phosphatides. Phosphorus-containing derivatives of lipids are known as phospholipids, and phosphoglycerides are one type of phospholipid. 

Figure 14-8. Phosphatidic acid and its derivatives. The 0 shown shaded in phosphatidic acid is substituted by the substituents shown to form in (A) 3-phosphatidylcholine, (B) 3-phosphatidylethanolamine,...

Organophilic polyphenolic materials for oil-based drilling fluids have been described [407], The additives are prepared from a polyphenolic material and one or more phosphatides. The phosphatides are phosphoglycerides obtained from vegetable oils, preferably commercial lecithin. Humic acids, ligno-sulfonic acid, lignins, phenolic condensates, tannins the oxidized, sulfonated, or sulfomethylated derivatives of these polyphenolic materials may serve as polyphenolic materials. 

The nomenclature for associating individual fatty acid groups with particular phosphodig-lyceride derivatives is straightforward. For instance, a phosphatidic acid (PA) derivative which contains two myristic acid chains is commonly called dimyristoyl phosphatidic acid (DMPA). Likewise, a PC derivative containing two palmitate chains is called dipalmitoyl phosphatidyl choline (DPPC). Other phosphodiglyceride derivatives are similarly named. 

The rate of production of DAG in the cell does not occur linearly with time, but rather it is biphasic. The first peak is rapid and transient and coincides with the formation of IP3 and the release of Ca2+ this DAG is therefore derived from the PI-PLC catalyzed hydrolysis of phosphatidylinositols [1]. There is then an extended period of enhanced DAG production that is now known to be derived from the more abundant phospholipid phosphatidylcholine (PC), which has a different composition of fatty acid side chains [9]. Although DAG may be generated directly from PC through the action of PC-PLC, it can also be formed indirectly from PC. In this pathway, PC is first hydrolyzed by PLD to give choline and phosphatidic acid, which is then converted to DAG by the action of a phos-phatidic acid phosphatase [10,11 ]. 

The first experiments implicating a role for PLD activity in neutrophil function were performed by Cockcroft and colleagues (Cockcroft Stutchfield, 1989 Cockcroft, 1992) who measured phosphatidic acid accumulation in cells whose membrane phospholipids or ATP were radiolabelled. These experiments showed that phosphatidic acid accumulation during cell activation did not derive from DAG, but rather was directly generated from a phospholipid. Phosphatidic acid production from DAG (generated by PLC)... 

Figure 12.11 Phosphoglyceride structure. The members of this group are derivatives of the parent compound, l,2-diacyl-src-glycerol-3-phosphate (phosphatidic acid) in which X is a hydrogen atom. This is replaced by either an amino alcohol or a polyhydroxy residue. In phosphoglycerides derived from animal tissues R1 is usually a saturated acyl chain of between 16 and 20 carbon atoms and R2 is usually unsaturated. Polyunsaturated acyl chains containing 16 or 18 carbon atoms predominate in leaf phosphoglycerides and those of bacterial origin are often more complex.

Table 12.5). Phosphoglycerides are derivatives of glycerophosphoric acid (l,2-diacyl-sn-3-phosphate) which is also called phosphatidic acid. 

The simplest of the glycerophospholipids is phosphatidic acid, in which phosphate is linked to the third hydroxyl function, forming a phosphate ester. More complex glycerophospholipids are derivatives of phosphatidic acid in which one of several groups is attached commonly choline, ethanolamine, serine, or myo-inositol. Structures are collected in table 19.1. 

The other phospholipids can be derived from phosphatidates (residue = phosphatidyl). Their phosphate residues are esterified with the hydroxyl group of an amino alcohol choline, ethanolamine, or serine) or with the cyclohexane derivative myo-inositol. Phosphatidylcholine is shown here as an example of this type of compound. When two phosphatidyl residues are linked with one glycerol, the result is cardiolipin (not shown), a phospholipid that is characteristic of the inner mitochondrial membrane. Lysophospholipids arise from phospholipids by enzymatic cleavage of an acyl residue. The hemolytic effect of bee and snake venoms is due in part to this reaction. 

Phosphatidylcholine (lecithin) is the most abundant phospholipid in membranes. Phosphatidylethanolamine (cephalin) has an ethanolamine residue instead of choline, and phosphatidylserine has a serine residue. In phosphatidylinositol, phosphatidate is esterified with the sugarlike cyclic polyalcohol myo-inositol. A doubly phosphorylated derivative of this phospholipid, phosphatidylinositol 4,5-bisphosphate, is a special component of membranes, which, by enzymatic cleavage, can give rise to two second messengers, diacylglycerol (DAG) and inositol l,4,5trisphosphate (InsPsi see p.386). 

Transfer of a phosphocholine residue to the free OH group gives rise to phosphatidylcholine (lecithin enzyme l-alkyl-2-acetyl-glycerolcholine phosphotransferase 2.7.8.16). The phosphocholine residue is derived from the precursor CDP-choline (see p. 110). Phos-phatidylethanolamine is similarly formed from CDP-ethanolamine and DAG. By contrast, phosphatidylserine is derived from phosphatidylethanolamine by an exchange of the amino alcohol. Further reactions serve to interconvert the phospholipids—e.g., phosphatidylserine can be converted into phosphatidylethanolamine by decarboxylation, and the latter can then be converted into phosphatidylcholine by methylation with S-adenosyl methionine (not shown see also p. 409). The biosynthesis of phosphatidylino-sitol starts from phosphatidate rather than DAG. 

The ozonides of choline and ethanolamine phosphatides and triglycerides can be subjected to reduction with triphenylphosphine to yield the corresponding core aldehydes, and further derivatized to the 2,4-dinitrophenylhydrazones (DNP). The core aldehydes and their DNP derivatives can be separated by HPLC and characterized by various techniques, including EI-MS and TS-MS of positive and negative ions . See also Section VHI.E. 

The last three sources are transported into the cell via inositol transporter [T]. Inositol combines with cytidine monophosphate phosphatidic acid [GMPPA] to be converted to PI, which is then phosphorylated to phos-phatidylinositol phosphate [PIP] and to PIP2 to be reused to form the PI cycle-derived second messengers IP3 and DAG [Kofman and Belmaker 1993]. 

The inositol phosphates are linked into a metabolic cycle (Fig. 6.5) in which they can be degraded and regenerated. Via these pathways, the cell has the ability to replenish stores of inositol phosphate derivatives, according to demand. Ptdins may be regenerated from diacylglycerol via the intermediate levels of phosphatidic acid and CDP-glycerol. 

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