Fatty acids, long-chain desaturation

FIGURE 3-7 Pathways for the interconversion of brain fatty acids. Palmitic acid (16 0) is the main end product of brain fatty acid synthesis. It may then be elongated, desaturated, and/or P-oxidized to form different long chain fatty acids. The monoenes (18 1 A7, 18 1 A9, 24 1 A15) are the main unsaturated fatty acids formed de novo by A9 desaturation and chain elongation. As shown, the very long chain fatty acids are a-oxidized to form a-hydroxy and odd numbered fatty acids. The polyunsaturated fatty acids are formed mainly from exogenous dietary fatty acids, such as linoleic (18 2, n-6) and a-linoleic (18 2, n-3) acids by chain elongation and desaturation at A5 and A6, as shown. A A4 desaturase has also been proposed, but its existence has been questioned. Instead, it has been shown that unsaturation at the A4 position is effected by retroconversion i.e. A6 unsaturation in the endoplasmic reticulum, followed by one cycle of P-oxidation (-C2) in peroxisomes [11], This is illustrated in the biosynthesis of DHA (22 6, n-3) above. In severe essential fatty acid deficiency, the abnormal polyenes, such as 20 3, n-9 are also synthesized de novo to substitute for the normal polyunsaturated acids. 

Wahle, K.W. 1974. Desaturation of long-chain fatty acids by tissue preparations of the sheep, rat and chicken. Comp. Biochem. Physiol. 48B, 87-105. 

As a result of impaired activity of acetyl CoA and propionyl CoA carboxylases, there are changes in the fatty acid composition of lipids in the lymphocytes of biotin-deficient rats. There is an increase in the proportion of long-chain fatty acids (C22 0 to C30 0) and odd-carbon fatty acids (Cl 5 0 to C29 0), with a decrease in the proportion of unsaturated fatty acids and the ratio of ds-vaccenic acid (C18 l )9) palmitoleic acid (C16 lft)6), which is indicative of impaired elongation and desaturation of fatty acids (Liu et al., 1994). 

Fig. 1. Metabolic pathway of essential fatty acids. Recent evidence indicated that 22 6n-3 are produced by [l-oxidation of 24 6n-3, which is desaturated from 24 5n-3, after elongation from 22 5n-3. Very long-chain fatty acids in the box are found in the retina however, the metabolism and function is not known.

Acyl-CoA molecules are desaturated in ER membrane in the presence of NADH and 02. All components of the desaturase system are integral membrane proteins that are apparently randomly distributed on the cytoplasmic surface of the ER. The association of cytochrome b5 reductase (a flavoprotein), cytochrome b5, and oxygen-dependent desaturases constitutes an electron transport system. This system efficiently introduces double bonds into long-chain fatty acids (Figure 12.15). Both the flavoprotein and cytochrome b5 (found in a ratio of approximately 1 30) have hydrophobic peptides that anchor the proteins into the microsomal membrane. Animals typically have A9, A6, and A5 desaturases that use electrons supplied by NADH via the electron transport system to activate the oxygen needed to create the double bond. Plants contain additional desaturases for the A12 and A15 positions. 

After fatty acid synthesis, downstream enzymes can further modify palmi-tate for various cellular functions. In the endoplasmic reticulum, the 16 carbon fatty acid can be modified to fatty acids with eighteen or more carbons known as very long chain fatty acids (VLCFA), such as stearate (18 0) by a family of elongase enzymes called elongation of very long chain fatty acids (ELOVLl-6) (Jakobsson et ah, 2006). Palmitate and stearate can also be desaturated by stearoyl-CoA desaturase-1 (SCDl) at the cis-9 carbon to palmitoleate (16 1) and oleate (18 1), respectively (Sampath and Ntambi,... 

Desaturation of long-chain fatty acids in mammals. 198... 

See also Fatty Acids, Table 10.1, Synthesis of Long Chain Fatty Acids, Fatty Acid Desaturation, Fatty Acid Synthase, Palmitate Synthesis from Acetyl-CoA... 

The long chain fatty acids synthesized by the chloroplast system are in the form of ACP derivatives. At any point in the fabrication of the chain there are four things that can happen to the acyl moiety 1) the acyl ACP can be utilized in another cycle of elongation, 2) the acyl chain can be transferred to glycerol-3-phosphate, 3) the acyl moiety can be exported from the chloroplast to the cytoplasmic compartment, and 4) the acyl ACP can be desaturated. (Figure 1 ). 

Following the discovery of peroxisomal long chain fatty acid P-oxidation in rat liver and its induction by hypolipidemic drugs, the involved enzjmes were characterized mainly by Hashimoto, Osumi and coworkers in hver from induced rats. This resulted in the following picture. After activation, the CoA-esters are desatured by an FAD-dependent acyl-CoA oxidase. The formed 2-trcms noy -CxiA is hydrated to a 3-L-hydrox-yacyl-CoA that is subsequently dehydrogenated to a 3-oxoacyl-CoA. These reactions are... 

A common chemical property of polyunsatured fatty acids, which are needed to maintain animals in healthy condition, seems to be cis double bonds at the w6 and w9 positions [14]. Important essential fatty acids in the diet are linoleic (18 2w6) and a-linoleic (18 3w3) acids, which both occur in plants. In the mammalian organism, these fatty acids can be desaturated and elongated to form the derived essential fatty acids, dihomo-y-linolenic acid (20 3w6), arachidonic acid (20 4 6) and timnodonic acid (20 5to3), the three precursor acids of prostaglandins (Fig. 2, see also Fig. 11). The derived essential fatty acids can also be obtained in the diet. Arachidonic and dihomo-y-linolenic acids occur in animal tissues timnodonic acid in fish. The mammalian organism cannot introduce double bonds at the co3 and <06 positions of long-chain fatty acids, which partly explains why fatty acids of the w3 and w6 series must be provided in the diet (see refs. 15-18 for reviews). These fatty acids are also essential to man, however, deficiency states can only be induced by... 

From hnolenic acid bishomo-y-linolenic acid (eicosatrienoic acid) is formed which may be desaturated to arachidonic acid (eicosatetraenoic acid) (Fig. 68) and eicosapentaenoic acid. Very long chain fatty acids are constituents of waxes (see Table 29). 

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