Metabolic fatty acids, molecular structures

In this chapter, molecular factors affecting structural behavior of fat polymorphism are discussed in terms of internal influences of the TAG molecules. In particular, the influences of fatty acid compositions and their positions connected to glycerol carbons on the polymorphism of fat crystals are of primary concern. It has been known that the fats with simple and symmetric fatty acid compositions tend to exhibit typical oc, P, and P forms, whereas those with asymmetric mixed-acid moieties often make the P form more stable (1,9). In the mixed-acid TAG containing unsaturated fatty acid moieties, the number and conformation of the double bond, cis or trans, give rise to remarkable influences on the polymorphic structures (10-12). The TAG containing different saturated fatty acids with different chain-lengths also revealed quite diversified polymorphism (13-15). Therefore, it may be worthwhile now to discuss the molecular aspects of the polymorphism of fats. This consideration may also be a prerequisite for molecular design of structured fats, in combination with nutritional and metabolic properties. 

In 1947 he isolated and named coenzyme A (or CoA) as well as determining the molecular structure (1953) of this factor that is now known to be bound to acetic acid as the end product of sugar and fat breakdown in the absence of oxygen. It is one of the most important substances involved in cellular metabolism, since it helps convert amino acids, steroids, fatty acids, and hemoglobins into energy. For his discovery of this coenzyme, he was awarded the 1953 Nobel Prize for physiology or medicine. He died on July 24, 1986, in Poughkeepsie, New York. 

The discovery of anandamide (arachidonoyl ethanolamide, AEA) and of its manifold roles in the central nervous system and in the periphery (reviewed in refs. 1 and 2) prompted several researchers to develop analytical methods to assay and characterize the activity of the enzymes responsible for AEA metabolism in various cells and tissues. Fatty acid amide hydrolase (arachidonoyl ethanolamide amidohydrolase, EC 3.5.1.4 FAAH) has emerged as the key AEA hydrolase, showing a molecular mass of approx 64 kDa and an optimum pH of around 9.0 (3). Recently, FAAH has been crystallized,and its three dimensional structure has been determined at 2.8A resolution (4). This enzyme cleaves the amide bond and releases arachidonic acid and ethanolamine. High-performance liquid chromatography (HPLC) is the most widely used method to determine FAAH activity from different sources. We developed a new method (5) based on reversed-phase (RP)-HPLC and on-line scintillation counting, which combines the need for high resolution, reproducibility, and sensitivity... 

Extracellular anandamide, after it serves its function, is rapidly taken up by neuronal and non-neuronal cells by a high-affinity carrier-mediated transport mechanism. This mechanism meets key criteria of carrier-mediated transport, such as fast rate (t, of approximately 4 min), temperature dependence, satura-bility, and substrate selectivity (Beltramo et ah, 1997 Hillard et al., 1997). Furthermore, the transportation of anandamide is independent of sodium ions and is not affected by metabolic inhibitors. The second endogenous camiabinoid, 2-AG, competes for uptake with anandamide. It has been variously reported to exhibit a 2-fold higher affinity for the anandamide transporter than anandamide (Jarrahian et al, 2000), or equal affinity (Piomelli et al, 1999). The molecular structure of this hypothetical anandamide transporter remains unknown. However, it is selective for fatty acid amides or esters, and it is not a fatty acid transporter (Piomelli et al, 1999 Jarrahian et al, 2000). Very recent results indicate that anandamide uptake is a process driven by metabolism and other downstream events, rather than by a specific membrane-associated anandamide carrier (Glaser et al, 2003). 

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