Fatty acids brain structure

FAAH was originally purified and cloned from rat liver microsomes and is able to catalyse the hydrolysis of anandamide and 2-AG, in addition to other long-chain fatty acid amides [25]. Studies into the structure and role of this enzyme have generated interest in the potential therapeutic applications of FAAH inhibitors [26-28]. FAAH knock-out mouse brains contained 15-fold higher levels of anandamide than their wild-type counterparts and these animals have also been shown to be more responsive to exogenously administered anandamide [29]. These animals also showed a reduced response to painful stimuli, supporting the hypothesis that FAAH inhibition may provide novel analgesics. Levels of 2-AG were not elevated in the FAAH knock-out animals, apparently due to the existence of alternative metabolic fates for this compound [30]. 

The hydrophobic components of many lipids consist of either isoprenoids or fatty acids and their derivatives 34 Isoprenoids have the unit structure of a five-carbon branched chain 34 Brain fatty acids are long-chain carboxylic acids that may contain one or more double bonds 34... 

Each phospholipid class in a given tissue has a characteristic fatty acid composition. Though the same fatty acid may be present in a number of lipids, the quantitative fatty acid composition is different for each class of lipids and remains fairly constant during the growth and development of the brain. A typical distribution profile of the major fatty acids in rat brain phospholipids is given in Table 3.1. Not only do the phosphoglycerides differ in the structure of the polar head groups, or phospholipid... 

Sterols are compounds that have a steroid structure (Figure 12.5) and contain a hydroxyl group, which is capable of forming an ester. They are widespread in nature and commonly exist as mixtures of the free sterol and esters with fatty acids. Cholesterol (Figure 12.5) is by far the commonest sterol in animals, a high concentration being found in brain, nervous tissue and membranes. Plants... 

Approximately 60% of the dry weight of the brain is fat, a considerable proportion of which is polyunsaturated fatty acids that are present in plasma membranes. It would not be surprising if replacement of the unsaturated acids by the saturated fatly acids in membrane structure due to a dietary deficiency of polyunsaturated fatty acids played some part in development of mental illness. Indeed, it has been found that supplementation of a normal diet with polyunsaturated fatly acids can improve some mental disorder (see chapter 11). 

Glycerophospholipids are present in a variety of tissues in the body but more particularly in nerve and brain. They are involved in several fundamental biochemical processes and much more work remains to be done to clarify both their complete function and structural content. As a class, they are fatty acids esters of esterified glycerophosphoric acid (12) and eliminate the phosphate ester group under GC conditions [283,284]. 

Oleamide, a lipid originally named cerebrodiene, was first iso lated from partially sleep-deprived cats (Lerner et al 1994). The molecule, with the chemical formula C18H35NO, is a long-chain base structurally related to sphingosine and sphinganine (Lerner et al 1994). Oleamide, or cerebrodiene, is chemically characterized as cis-9,10-octadecenoamide (Cravatt et al 1995). Oleamide is degraded by the brain enzyme fatty acid amide hydrolase (FAAH), which also degrades anandamide (Cravatt et al. Nature 1996). 

Blount, B.K. Robinson, R. Derivatives of 1-Methyltropane 1933 Boger, L. R. Inhibitors of Fatty Acid Amide Hydrolase 2002 US 6,462,054 Boring D.L, Berglund, B.A, Howlett A.C. Cerebrodiene, Arachidonyl-ethanolamide, and Hybrid Structures Potential for Interaction with Brain Cannabinoid Receptors Prostaglandins Leukot Essent Fatty Acids. (1996) 55(3) 207-10. 

Biedermann, W., Lucker, E., Porschmann, J., Lachaab, S., Truyen, U., and Hensel, A. 2004. Structural characterization of some fatty acids from the brain as biomarkers of BSE risk material. Anal. Bioanal. Chem. 379,1031-1038. 

Connor WE, Neuringer M. The effects of n-3 fatty acid deficiency and repletion upon the fatty acid composition and function of the brain and retina. In Kamovsky ML, Leaf A, Bolis LC, eds. Biological Membranes Aberrations in Membrane Structure and Function. Alan R Liss, New York, 1988, pp. 275-294. 

---