Phospholipids remodeling

Phospholipids can be synthesized by a number of different routes. However, the primary synthesis route is relatively unimportant because the final structures of brain phospholipids are largely determined not by the structure first synthesized but by the highly active and constant phospholipid remodeling that goes on within the brain. This remodeling plays a central role in several signal transduction cycles, which will be summarized in the following subsections. 

The y-isoenzyme lacks the C2 domain, is prenylated at the C-terminus, and lacks the regulatory phosphorylation sites of cPLAja. The enzyme demonstrates high lysophospho-lipase activity and lacks the acyl chain selectivity of the a-isoenzyme suggesting a role in phospholipid remodeling [23]. The 6, e, and -isoezymes have been identified more recently (H. Chiba, 2004 T. Ohto, 2005) and are discussed [23]. The group IV isoenzymes (a- ) have also been designated A-F [15]. 

Balsinde, J., I. D. Bianco et al. 1995. Inhibition of calcium-independent phosphohpase A2 prevents arachidonic acid incorporation and phospholipid remodeling in P388D1 macrophages. 92(18) 8527-8531. 

When fibroblasts are infected in vitro with CMV, US28 RNA can be detected only during the late phase (90). Some of the biochemical changes that occur in infected fibroblasts are the same as those induced by chemokine signaling in leukocytes (e.g. Ca " mobilization and phospholipid remodeling), and inhibition of these changes markedly... 

The pathway for the synthesis of dipalmitoyl-phos-phatidylcholine is illustrated in figure 19.5. The starting species of phosphatidylcholine is made by the CDP-choline pathway (see fig. 19.4). The fatty acid at the sn-2 position, which is usually unsaturated, is hydrolyzed by phospholi-pase A2, and the lysophosphatidylcholine is reacylated with palmitoyl-CoA. This modification permits alteration of the properties of the phospholipid without resynthesis of the entire molecule, a strategy called remodeling. Deacylation-reacylation of phosphatidylcholine occurs in other tissues and provides an important route for alteration of the fatty acid substituents at both the sn-1 and sn-2 positions. For example, fatty acids at the sn-2 position can be replaced by arachidonic acid, which is stored there until needed for eicosanoid biosynthesis, as we discuss later in this chapter. 

In some cases the functions of phospholipases in cells are purely degradative and result in the release of the phospholipid components (fatty acids, glycerol, phosphate, and head-groups). But in many cases phospholipases have important roles in synthesis and regulation. For example, we have seen how phospholipase A2 catalyzes the first step in the remodeling of phosphatidylcholine to the surfactant... 

Rapoport S. I. (1999). In vivo fatty acid incorporation into brain phospholipids in relation to signal transduction and membrane remodeling. Neurochem. Res. 24 1403-1415. 

Fatty acids are incorporated into complex lipids through de novo synthetic and remodeling pathways. As detailed below and shown in Fig. 2a, intracellular pools of acyl-CoA are involved in processes outside of lipid metabolism and, in many instances, function as important regulatory molecules. Figure 2b illustrates an overview of glycerol phospholipid synthesis and how fatty acids in the form of acyl-CoA enter these metabolic pathways. Readers are referred to the article entitled Lipid Synthesis in this series for specific details regarding these pathways. 

This critical review describes an experimental method and mathematical model to quanfily in vivo incorporation rates, half-lives, and turnover rates of FAs into brain phospholipids. FA incorporation is independent of cerebral blood flow and is thus a direct measure of brain phospholipid metabolism. Because specific FAs enter specific phospholipids at stereospecific positions, a combination of saturated and polyunsaturated FA labels can he used to investigate the active participation of phospholipids in brain signal transduction, membrane remodeling, and neuroplasticity. 

Dramatic changes in the fatty acids of the frontal cortex were detected within 1 wk after the fish-oil diet was given as demonstrated in the individual data in the frontal lobe biopsy specimens from five juvenile monkeys. All four major phospholipid classes of the brain underwent extensive remodeling of their constituent fatty acids. The data in Fig. 3 is for the fatty acids of phosphatidylethanolamine from each of the five experimental monkeys. By 12-28 wk, the total n-3 fatty acids increased from 4% to 36%of total fatty acids (Connor et al., 1990b). The major increase was in DHA, from 4% to 29%, whereas EPA and 22 5n-3, another n-3 fatty acid found in fish oil, each increased from 0% to almost 3%. To be emphasized, as will be discussed later, is the apparent conversion of EPA to DHA in the brain. The total n-6 fatty acids reciprocally decreased from 44% to 16% of the total fatty acids, with the major reduction occurring in 22 5n-6, from 18% to 2%, and 22 4n-6, from 12% to 4%. There was also a moderate decrease of arachidonic acid from 12.8% to 8.9% of total fatty acids. Again, a major remodeling of the phospholipid fatty acids from n-6 to n-3 fatty acids was evident. 

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