Long-chain fatty acids roles

Dutta-Roy, A.K. (2000) Cellular uptake of long chain fatty acids role of membrane associated fatty acid binding/transport proteins. Cellular and Molecular Life Sciences (in press). 

Kim, K-H., et al., 1989. Role of rever.sible pho.sphorylation of acetyl-CoA carboxyla.se in long-chain fatty acid. syndie.sis. The EASEB Journal 3 22 0-2256. 

Figure 22-1. Role of carnitine in the transport of long-chain fatty acids through the inner mitochondrial membrane. Long-chain acyl-CoA cannot pass through the inner mitochondrial membrane, but its metabolic product, acylcarnitine, can. 

The free fatty acid uptake by tissues is related directly to the plasma free fatty acid concentration, which in turn is determined by the rate of lipolysis in adipose tissue. After dissociation of the fatty acid-albumin complex at the plasma membrane, fatty acids bind to a membrane tty acid transport protein that acts as a transmembrane cotransporter with Na. On entering the cytosol, free fatty acids are bound by intracellular fatty acid-binding proteins. The role of these proteins in intracellular transport is thought to be similar to that of serum albumin in extracellular transport of long-chain fatty acids. 

These are the esters of long-chain fatty acids and long-chain fatty alcohols. Usually, only the alcohols are saturated and monoenoic, whereas the fatty adds may be more highly unsaturated, as in most marine waxes. They are found in both animal and plant tissues as well as in some microorganisms. They are quite common in insects. They reserve energy in aquatic animals, aid in echolocation, and play a vital role in waterproofing. 

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]. 

Carnitine is a vitamin-like quaternary ammonium salt, playing an important role in the human energy metabolism by facilitating the transport of long-chained fatty acids across the mitochondrial membranes. An easy, fast, and convenient procedure for the separation of the enantiomers of carnitine and 0-acylcarnitines has been reported on a lab-made teicoplanin-containing CSP [61]. The enantioresolution of carnitine and acetyl carnitine was enhanced when tested on a TAG CSP, prepared in an identical way [45]. Higher a values were reached also in the case of A-40,926 CSP [41]. 

The capacity of P-oxidation in about 10% of that in the mitochondria but it plays an important role in oxidising unusual fatty acids for example, very long-chain fatty acids, polyunsaturated fatty acids, dicarbox-ylic fatty acids. 

Table 11.1 Summary of the roles of long-chain fatty acids...

The most frequent protein in the plasma, at around 45 g is albumin. Due to its high concentration, it plays a crucial role in maintaining the blood s colloid osmotic pressure and represents an important amino acid reserve for the body. Albumin has binding sites for apolar substances and therefore functions as a transport protein for long-chain fatty acids, bilirubin, drugs, and some steroid hormones and vitamins. In addition, serum albumin binds Ca "" and Mg "" ions. It is the only important plasma protein that is not glycosylated. 

Deschamps, D. et al. (1991) Inhibition by salicylic acid of the activation and thus oxidation of long chain fatty acids. Possible role in the development of Reye s syndrome. Journal of Pharmacology and Experimental Therapeutics, 259 (2), 894-904. 

In insects, especially Diptera, several pioneer studies reviewed by Blomquist et al. (1987) established that long chain hydrocarbons, some of which play a pheromone role, were derived from very long chain fatty acids by reduction and decarboxylation. Thus, pheromone biosynthesis shares steps with those leading to basic lipid molecules and also with those of the well-known pheromones of Lepidoptera (Roelofs and Wolf, 1988). All often display several double bonds located in various positions while the volatile butterfly compounds bear functional groups (acetate, aldehyde or alcohol) and aliphatic chains with 12-16 carbons. Contact pheromones of flies have much longer chains (21C-39C) (Pennanec h et al., 1991). 

Cobum C. T., HajriT., Ibrahimi A. and Abumrad N. A. (2001) Role of CD36 in membrane transport and utilization of long-chain fatty acids by different tissues. J. Mol. Neurosci. 16, 117-121 discussion 151-157. 

Tvrdik, P., Westerberg, R., Silve, S., Asadi, A., Jakobsson, A., Cannon, B., Loison, G. and Jacobsson, A. (2000). Role of a new mammalian gene family in the biosynthesis of very long chain fatty acids and sphingolipids../. Cell Biol., 149, 707-718. 

Kim KH, Lopez-Casillas F, Bai DH, Luo X, Pape ME. Role of reversible phosphorylation of acetyl-CoA carboxylase in long-chain fatty acid synthesis. FASEB J 3 2250-2256, 1989. 

Figure 9-1- Role of carnitine in fatty acid oxidation. Long-chain fatty acids are activated as the thioester of CoA on the cytoplasmic side of the mitochondrial membrane. The fatty acyl group is then transferred to form the corresponding carnitine ester in a reaction catalyzed by carnitine palmitoyltransferase I (CPT ]) The acylcarnitine then enters the mitochondrial matrix in exchange for carnitine via the carnitine-acylcarnitine translocase. The acyl group is transferred back to CoA in the matrix by carnitine palmitoyltransferase II (CPT II). The intramitochondrial acyl-CoA can then undergo P-oxidation.

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