Phosphatidyl compounds

The final region from -2.00 to 0.00 ppm is attributed to diester phosphates such as RNA, DNA, nucleotide fragments, and phosphatidyl compounds. Signals occur in this region for both DNA and phosphatidyl choline in a concentrated humic matrix with FeEDTA present (Figure 11). 3IP FT-NMR evidence supporting the presence of DNA is provided by the spectrum of a sample that has been oxidized by alkaline bromination (Figure 12). 

Most phospholipids are essentially disubstituted phosphates (Figure 1.27). They may be initially classified as phosphatidyl compounds, plasmalogens, ether phospholipids and sphingomyelins depending on the nature of the Ri group attached to the phosphate residue (Table 1.6). 

Sphingomyelins are phosphorus-containing members of the second large class of membrane lipids known as sphingolipids (10.50b). The head group X is most commonly choline or ethanolamine, and these compounds resemble the corresponding phosphatidyl compounds (10.47) in their general... 

Lecithin. Lecithin [8002-43-5] (qv) is a mixture of fat-like compounds that includes phosphatidyl choline, phosphatidyl ethanolamines, inositol phosphatides, and other compounds (37). Commercial lecithin was originally obtained from egg yolks, but is now extracted from soybean oil. Lecithin is used in many products, including margarine, chocolate, ice cream, cake batter, and bread. 

Modulation of second-messenger pathways is also an attractive target upon which to base novel antidepressants. Rolipram [61413-54-5] an antidepressant in the preregistration phase, enhances the effects of noradrenaline though selective inhibition of central phosphodiesterase, an enzyme which degrades cycHc adenosiae monophosphate (cAMP). Modulation of the phosphatidyl iaositol second-messenger system coupled to, for example, 5-HT,, 5-HT,3, or 5-HT2( receptors might also lead to novel antidepressants, as well as to alternatives to lithium for treatment of mania. Novel compounds such as inhibitors of A-adenosyl-methionine or central catechol-0-methyltransferase also warrant attention. 

Italic indicates compounds are in therapeutic use. PI, phosphatidyl inositol. 

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. 

The anandamide precursor, phosphatidylethanol amine, is present in membranes almost always accompanied by phophatidylserine. It seemed reasonable to expect the formation of anandamide from its precursor will be paralleled by formation of N-arachidinoylserine from phosphatidyl serine. Indeed, A -arachidonoyl-L-serine (ARA-S) was found to be formed alongside anandamide (Fig. 4). This compound was isolated from bovine brain and its structure was elucidated by comparison with synthetic ARA-S. Contrary to anandamide, ARA-S binds very weakly to the known cannabinoid CBi and CB2 or vanilloid TRPVl receptors. However, it produces endothelium-dependent vasodilation of rat isolated mesenteric... 

Inositol-containing phospholipids of the plasma membrane are the starting compounds for formation of the signal substances diacylglycerol and inositol trisphophate. The plasma membrane contains the phospholipid phosphatidyl inositol, in which the phosphate group is esterified with a cychc alcohol, myo-D-inositol (Fig. 6.3). 

Several metabohc pathways lead from phosphatidyl inositol to compounds with second messenger" character (review Liscovitch and Cantley, 1994 Divecha and Irvine, 1995). One main pathway, the formation of diacylglycerol and Ins(l,4,5)P3 from PtdIns(4,5)P2, has already been described in 6.4 and Fig. 6.3. Other compounds of regulatory importance can be formed by phosphorylation at the 3 position of the inositol part of Ptdins (Fig. 6.9). The reaction is catalyzed by a class of enzymes known as phosphatidylinositide 3-kinases (P13-kinases). The P13-kinases phosphorylate various phosphatidyl inositol compoimds at the 3 position. For example, PtdIns(3,4,5)P3, produced by 3 phosphorylation of Ptdlns(4,5)P2, has an important function as an intracellular messenger (see 6.6.2). 

Fig. 6.9. A) Metabolism of phosphatidyl inositol lipids. The figure shows different membrane-associated phosphatidyl inositol phosphate compounds and their mutual conversion. PI3-kinase (PI3K) is responsible, in particular, for the formation of PtdIns(3,4,5)P3 from PtdIns(3,4)P2. For the reactions marked with a question mark, involvement of PI(3) kinase is not certain.

Several studies have evaluated the effects of oral di(2-ethylhexyl) adipate on various aspects of hepatic lipid metabolism. Feeding di(2-ethylhexyl) adipate (2% of diet) to male Wistar rats for seven days resulted in increased hepatic fatty acid-binding protein as well as in increased microsomal stearoyl-CoA desaturation activity (Kawashima et al., 1983a,b). Feeding the compound at this dose for 14 days resulted in increased levels of hepatic phospholipids and a decline in phosphatidyl-choline phosphatidylethanolamine ratio (Yanagita et al., 1987). Feeding di(2-ethyl-hexyl) adipate (2% of diet) to male NZB mice for five days resulted in induction of fatty acid translocase, fatty acid transporter protein and fatty acid binding protein in the liver (Motojima et al., 1998). 

Studies of the pharmacokinetics of silymarin and of a silibinin-phosphatidyl-choline complex preparation (IdB 1016 silipide) in humans as well as rodents have been performed. Because silibinin is the main compound, pharmacokinetic parameters of silymarin and the active principle of any silymarin-containing products are always referred to, and standardized, as silibinin. 

Incorporation of phosphatidyl choline and AMP signals into the large, broad envelope was unexpected because it had not been observed before with studies involving model compounds in a concentrated humic matrix with FeEDTA present (44). However, these model compound studies were conducted at a phosphorus concentration of 150 mg of P/L, a concentration 10 times greater than the amount that was spiked into sample I. This fact,... 

Recent work indicates that various methylarsenic compounds can be accumulated by marine organisms. These include arsenobetaine (2/0, 25/), trimethylarsoniumlactate [(CH3)3AsCH2CH(0H)C02] and its phosphatidyl derivatives (252-254), and arsenosugars (255), These compounds form from arsenate salts, and provide strong evidence for the biological formation of As-C bonds other than As-CH3. 

---