Brain lipids structures

A solution of brain lipids was brushed across a small hole in a 5-ml. polyethylene pH cup immersed in an electrolyte solution. As observed under low power magnification, the thick lipid film initially formed exhibited intense interference colors. Finally, after thinning, black spots of poor reflectivity suddenly appeared in the film. The black spots grew rapidly and evenutally extended to the limit of the opening (5, 10). The black membranes have a thickness ranging from 60-90 A. under the electron microscope. Optical and electrical capacitance measurements have also demonstrated that the membrane, when in the final black state, corresponds closely to a bimolecular leaflet structure. Hence, these membranous structures are known as bimolecular, black, or bilayer lipid membranes (abbreviated as BLM). The transverse electrical and transport properties of BLM have been studied usually by forming such a structure interposed between two aqueous phases (10, 17). 

Figure 10. Electron micrograph of brain lipid surface film formed in presence of Ca2+ and ATP. Presence of myelin-like laminar structure indicated by arrow, X 22,500...

Because altered sodium channels have been implicated in kdr and kdr-like resistance phenomena in insects, basic research on the biochemistry and molecular biology of this molecule, which plays a central role in normal processes of nervous excitation in animals, is of immediate relevance. The results of recent investigations of the voltage-sensitive sodium channels of vertebrate nerves and muscles have provided unprecedented insight into the structure of this large and complex membrane macromolecule. Sodium channel components from electric eel electroplax, mammalian brain, and mammalian skeletal muscle have been solubilized and purified (for a recent review, see Ref. 19). A large a subunit (ca. 2 60 kDa) is a common feature of all purified channels in addition, there is evidence for two smaller subunits ( Jl and J2 37-39 kDa) associated with the mammalian brain sodium channel and for one or two smaller subunits of similar size associated with muscle sodium channels. Reconstitution experiments with rat brain channel components show that incorporation of the a and pi subunits into phospholipid membranes in the presence of brain lipids or brain phosphatidylethanolamine is sufficient to produce all of the functional properties of sodium channels in native membranes (AA). Similar results have been obtained with purified rabbit muscle (45) and eel electroplax (AS.) sodium channels. 

It seems that a large proportion of adult rat, rabbit, or chicken brain cholesterol undergoes very slow metabolism. Since about 70% of brain cholesterol is located in the myelin sheath, it is probable that at least part of this structure is metabolically a relatively stable tissue component. Other studies on brain lipids support this view. Thus distribution of rat brain cerebroside sulfate is similar to that of cholesterol and turnover of sulfatide is also exceedingly slow. Furthermore, Davison and Gregson (1962) found that persisting radioactivity was associated primarily with the myelin fraction prepared from brains of rats previously injected with S -sulfate or methionine. 

Different animal species eat different foods in which the fatty acids vary considerably. Adaptation to different food structures throughout evolution could have led either to differences in brain lipids or, if the resistance to change was sufficiently great, the same lipid profile would evolve, but associated with differnet degrees of brain development. In this paper we wish to present data from a comparative analysis of 45 different animal species together with results obtained from the study of the fetal accumulation of the brain EFA in the human and in the guinea-pig. 

A great deal of research from several laboratories, including ours, has given a picture, incomplete, to be sure, of the many reactions that combine to determine the composition of the brain lipids. These are outlined in Fig, 1, which provides an overview of the sources and metabolic transformations of the fatty acids that contribute their properties to the major phosphoglycerides and sphingolipids that form the chief structural units of the membranes that are involved in most of the properties of the brain. 

Brain tissue had a special chemical composition. In the adult it contained more lipids than proteins and little glycogen. Little was known about the proteins, except for the recent findings of an active metabolism of nucleoproteins, presumably the underlying mechanism of chromatolysis. Lipids belonged to the structural, not the metabolic reserve pool, and an adult animal starved to death showed the same amount of brain lipids as its litter mate that had been fed properly. Much work had been done for several generations on the chemistry of brain lipids since they were often quite difierent from those found in other tissues. Their function was a puzzle they obviously acted as insulators in myelin and they provided anionic charges to the acid-base equilibrium of the tissue. Beyond that, they could only be supposed to play an active if as yet undefined role in the functioning of nervous membranes. 

Cerruti, C.D., Benabdellah, R, Laprevote, O., Touboul, D. and Brunelle, A. (2012) MALDI imaging and structural analysis of rat brain lipid negative ions with 9-aminoacridine matrix. Anal. Chem. 84, 2164-2171. 

As repeatedly stated in this book, the brain is a lipid machine with approximately 50% of its organic matter composed of lipids. To complicate tiie problem, lipids display broad biochemical diversity, allowing endless variations, from the more subtle (e.g., a-hydroxylation of the acyl chain of GalCer) to the more extreme (compare the structure of GTlb with that of cholesterol). To get a better idea of the situation, representative examples of closely related and totally unrelated lipid structures are given in Fig. 4.1. 

The book has been written to provide a hands-on approach for neuroscience graduate students. Biochemical structures are dissected and explained with molecular models. Moreover, we propose a step-by-step guide to memorize and draw the biochemical structure of brain lipids, including cholesterol and complex gangliosides. To conclude the book, we present new ideas that can drive innovative tiierapeutic strategies based on the knowledge of the role of lipids in brain disorders. 

Blocking the conversion to DA would appear stupid unless this could be restricted to the periphery. More dopa would then be preserved for entry into the brain, where it could be decarboxylated to DA as usual. Drugs like carbidopa and benserazide do precisely that and are used successfully with levodopa. They are known as extracerebral dopa decarboxylase inhibitors (ExCDDIs). Carbidopa (a-methyldopa hydrazine) is structurally similar to dopa but its hydrazine group (NHNH2) reduces lipid solubility and CNS penetration (Fig. 15.4). 

The lipid compositions of plasma membranes, endoplasmic reticulum and Golgi membranes are distinct 26 Cholesterol transport and regulation in the central nervous system is distinct from that of peripheral tissues 26 In adult brain most cholesterol synthesis occurs in astrocytes 26 The astrocytic cholesterol supply to neurons is important for neuronal development and remodeling 27 The structure and roles of membrane microdomains (rafts) in cell membranes are under intensive study but many aspects are still unresolved 28... 

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