Phospholipids in brain

Stangl, G.I. and M. Kirchgessner. 1997. Effect of nickel deficiency on fatty acid composition of total lipids and individual phospholipids in brain and erythrocytes of rats. Nutr. Res. 17 137-147. 

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. 

Of other acidic phospholipids tested by Vogt (1960) for activity toward smooth muscle, a lysophosphatidic acid had the greatest activity (cf. Table III). The presence of this phospholipid in brain extracts has... 

We describe the utility of intermediate-pressure MALDI and tandem mass spectrometry (MS/MS and MS ) for the characterization and imaging of phospholipids in brain tissue sections. The use of both MS/MS spectra and MS/MS images allows for identification of isobaric compounds. The structural characterization of phosphatidylcholines, phosphatidylserines, phosphatidylethanolamines, and sphingomyelins directly fi om tissue sections is described. 

It appears from the reported data that manipulations of dietary levels of EFA not only modify the PUFA content of structural phospholipids in brain, but also influence the rate of prostaglandin formation. 

Sphingomyelins are the second major group of phospholipids. These compounds have sphingosine or a related dihydroxyamine as their backbone and are particularly abundant in brain and nerve tissue, where they are a major constituent of the coating around nerve fibers. 

These compounds constimte as much as 10% of the phospholipids of brain and muscle. StmcmraUy, the plasmalogens resemble phosphatidylethanolamine but possess an ether link on the sn- carbon instead of the ester link found in acylglycerols. Typically, the alkyl radical is an unsamrated alcohol (Figure 14-10). In some instances, choline, serine, or inositol may be sub-stimted for ethanolamine. 

Phospholipids in synaptic membranes are an important target in seizures, head injury, neurodegenerative diseases and cerebral ischemia. Synaptic membranes are excitable membranes enriched in phospholipids esterified with the polyunsaturated fatty acids AA and DHA which form a significant proportion of the FFAs rapidly released during ischemia, seizure activity and other brain trauma. 

Multinuclear MRS studies have demonstrated alterations in brains of schizophrenic patients. Phosphorus MRS studies, looking at both first-onset-unmedicated and chronic-medicated schizophrenia, consistently report alterations in the phospholipid profile in the frontal and temporal cortex [26-30]. Typically, phosphomonoester (PME) levels are lower than in controls, and phosphodiesters... 

Pettegrew, J. W., Keshavan, M. S., Panchalingam, K. et al. Alterations in brain high-energy phosphate and membrane phospholipid metabolism in first-episode, drug-naive schizophrenics. A pilot study of the dorsal prefrontal cortex by in vivo phosphorus 31 nuclear magnetic resonance spectroscopy. Arch. Gen. Psychiat. 48 563-568,1991. 

Linamurin is the principal cyanogenic glycoside in cassava its toxicity is due to hydrolysis by intestinal microflora releasing free cyanide (Padmaja and Panikkar 1989). Rabbits (Oryctolagus cuniculus) fed 1.43 mg linamurin/kg BW daily (10 mg/kg BW weekly) for 24 weeks showed effects similar to those of rabbits fed 0.3 mg KCN/kg BW weekly. Specihc effects produced by linamurin and KCN included elevated lactic acid in heart, brain, and liver reduced glycogen in liver and brain and marked depletion in brain phospholipids (Padmaja and Panikkar 1989). 

Fig. 2.4. Schematic model of the molecular polymorphism of acetylcholinesterase and cholinesterase [110][112a]. Open circles represent the globular (G) catalytic subunits. Disulfide bonds are indicated by S-S. The homomeric class exists as monomers (Gl), dimers (G2), and tetramers (G4) and can be subdivided into hydrophilic (water-soluble) and amphiphilic (membrane-bound) forms. The G2 amphiphilic forms of erythrocytes have a glycophospholipid anchor. The heteromeric class exists as amphiphilic G4 and as asymmetric forms (A) containing one to three tetramers. Thus, heteromeric G4 forms found in brain are anchored into a phospholipid membrane through a 20 kDa anchor. The asymmetric A12 forms have three hydrophilic G4 heads linked to a collagen tail via disulfide bonds.

Kakela R, Somerharju P, Tyynela J. 2003. Analysis of phospholipids molecular species in brains from patients with infantile and juvenile neuronal-ceroid lipofuscinosis using liquid chromatography-electrospray ionization mass spectrometry. J Neurochem 84 1051. 

In view of these factors, it has been suggested that a deficiency of omega-3 fatty acid in the diet will decrease the concentration of these fatty acids available for synthesis of the required phospholipids in the body, including the brain. If this was a chronic deficiency it could increase the risk of development of some disorders, including depression, schizophrenia and attention deficit syndrome. There is some evidence that this is the case. 

To date the evidence seems to favor the binding of tumor promoter to phospholipid in the cell membrane. Specific binding of [3h]TPA to mouse epidermal particulate matter is susceptible to phospholipases C and A2, less susceptible to protease, and completely resistant to glycosidase (32). Photoaffinity labelling studies with [20-3h]-phorbol 12-p-azidobenzoate 13-benzoate indicates that the irreversible binding of this photolabile phorbol ester to mouse brain membrane is predominantly to the phospholipid (specifically phosphatidylethanolamine and phosphatidylserine) portion rather than to the protein portion (33). 

The adsorption of ATP-14C to surface films of stearic acid and brain lipid was examined over an extended period of time under various conditions (Table I and Figure 6B). Table I shows the short-term results, where adsorption was studied during the first 30 minutes, and evaporation was not a factor. Upon adding stearic acid or brain lipid the measurable radioactivity decreased, probably as a result of displacement of ATP-14C from the surface layer and self-absorption of the beta particles by the lipid film. When PMCG was present, there was a slight but significant increase in the surface adsorption of ATP. The amount of ATP adsorbed was 4 X 10 10 moles/sq. cm. for stearic acid and 2.5 X 10"10 moles/sq. cm. for brain lipid. If the lipid concentration in the surface is assumed to be about 8 X 10 10M (as phospholipid in the case of brain lipid), the molar ratio of ATP to lipid would be about 0.5 for stearic acid and 0.3 for brain lipid. 

Recent interest has focused on the C20 5 eicosa-pentaenoic acid (EPA) and the C22 6 docosa-hexaenoic acids (DHA). These 3 (or n-3) polyunsaturated acids are formed from linolenic acid by marine algae and are found in fish oils.h The C22 5 and C22 6 acids can be converted to prostaglandins of the PG4 and PG5 series. DHA together with the 0)6 C22 4 acid constitutes over 30% of the fatty acids in brain phospholipids. In the... 

Lipid peroxidation is one of the major sources of free-radical mediated injury that directly damages membranes and generates a number of secondary products. In particular, markers of lipid peroxidation have been found to be elevated in brain tissues and body fluids in several neurodegenerative diseases, and the role of lipid peroxidation has been extensively discussed in the context of their pathogenesis. Peroxidation of membrane lipids can have numerous effects, including increased membrane rigidity, decreased activity of membrane-bound enzymes (e.g., sodium pumps), altered activity of membrane receptors, and altered permeability [Anzai et al., 1999 Yehuda et al., 2002], In addition to effects on phospholipids, lipid-initiated radicals can also directly attack membrane proteins and induce lipid-lipid, lipid-protein, and protein-protein cross-linking, all of which obviously have effects on membrane function. 

Farooqui A. A. and Horrocks L. A. (2007a). Glutamate and cytokine-mediated alterations of phospholipids in head injury and spinal cord trauma. In Banik N. (ed.), Brain and Spinal Cord Trauma. Handbook of Neurochemistry. Lajtha, A. (ed.). Springer, New York, in press. 

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