Fatty acid elongation

Sites of further fatty acid elongation and desaturation... 

A second enzyme (of mass 100 kDa) is needed for activation of phenylalanine. It is apparently the activated phenylalanine (which at some point in the process is isomerized from l- to D-phenylalanine) that initiates polymer formation in a manner analogous to that of fatty acid elongation (Fig. 17-12). Initiation occurs when the amino group of the activated phenylalanine (on the second enzyme) attacks the acyl group of the aminoacyl thioester by which the activated proline is held. Next, the freed imino group of proline attacks the activated valine, etc., to form the pentapeptide. Then two pentapeptides are joined and cyclized to give the antibiotic. The sequence is absolutely specific, and it is remarkable that this relatively small enzyme system is able to carry out each step in the proper sequence. Many other peptide antibiotics, such as the bacitracins, tyrocidines,215 and enniatins, are synthesized in a similar way,213 216 217 as are depsipeptides and the immunosuppresant cyclosporin. A virtually identical pattern is observed for formation of polyketides,218 219 whose chemistry is considered in Chapter 21. 

Enzyme complexes occur in the endoplasmic reticulum of animal cells that desaturate at A5 if there is a double bond at the A8 position, or at A6 if there is a double bond at the A9 position. These enzymes are different from each other and from the A9-desaturase discussed in the previous section, but the A5 and A6 desaturases do appear to utilize the same cytochrome b5 reductase and cytochrome b5 mentioned previously. Also present in the endoplasmic reticulum are enzymes that elongate saturated and unsaturated fatty acids by two carbons. As in the biosynthesis of palmitic acid, the fatty acid elongation system uses malonyl-CoA as a donor of the two-carbon unit. A combination of the desaturation and elongation enzymes allows for the biosynthesis of arachidonic acid and docosahexaenoic acid in the mammalian liver. As an example, the pathway by which linoleic acid is converted to arachidonic acid is shown in figure 18.17. Interestingly, cats are unable to synthesize arachidonic acid from linoleic acid. This may be why cats are carnivores and depend on other animals to make arachidonic acid for them. Also note that the elongation system in the endoplasmic reticulum is important for the conversion of palmitoyl-CoA to stearoyl-CoA. 

Oh C. S., Toke D. A., Mandala S. and Martin C. E. (1997) EL02 and EL03, homologues of the Saccharomyces cerevisiae ELOl gene, function in fatty acid elongation and are required for sphingolipid formation. J. Biol. Chem. 272, 17376-17384. 

For each of the seven rounds of fatty acid elongation, one ATP is used in the synthesis of malonyl-CoA and two NADPH are used in the reduction reactions. 

Know pathways and attendant cofactors and key enzymes for fatty acid biosynthesis ketone body biosynthesis, utilization, and clinical implications and fatty acid elongation and unsaturation mechanisms. 

Heath, R.J. and C.O. Rock. 1995. Enoyl-acyl carrier protein reductase (fabl) plays a determinant role in completing cycles of fatty acid elongation in Escherichia coli. J. Biol. Chem. 270, 26538-26542. 

If the Fatty Acid Synthetase Complex only makes palmitate where do the rest of the fatty acids come from Of course palmitate can be shortened by P-oxidation. For longer fatty acids there is a fatty acid elongation system localized on the ER. The same reactions occur as in the S)mthetase, but now have individual enzymes. Palmitate is first activated to palmitoyl-CoA. The enzymes prefer C-16 or less as... 

A second system for fatty acid elongation exists in the mitosol, probably for provision of long fatty acids for mitochondrial structure. This system uses most of the same activities of 9-oxidation, but an NADPH dependent Enoyl-CoA reductase replaces the FAD dependent dehydrogenase. 

Methylene interrupted double bonds Due to the fatty acid elongation process during their synthesis, the double bonds are separated by one methylene group (spaced by three carbons)... 

In some insects, fatty acid elongation followed by decarboxylation produces the hydrocarbon pheromones, and these include examples of lepidopterans (Jurenka), dipterans [71], the German cockroach [72a] (see Fig. 6) and the social insects [73]. More recent work in bark beetles has shown that Ips and Dendroctonus spp. produce their monoterpenoid-derived pheromones ipsenol, ipsdienol and frontalin by modifications of... 

St. John, L.C., Lunt, D.K., and Smith, S.B. 1991. Fatty acid elongation and desaturation enzyme activities of bovine liver and subcutaneous adipose tissue microsomes. J. Anim. Sci. 69,... 

Fatty acid elongation Carnitine Aspartate aminotransferase... 

Mitochondrial fatty acid elongation occurs primarily when the [NADH]/[NAD+] ratio is high (e.g., anaerobiosis, excessive ethanol oxidation). 

The answer is d. (Murray, pp 230-267. Scriver, pp 2297-2326. Sack, pp 121-138. Wihon, pp 287-320.) In humans, the end product of fatty acid synthesis in the cytosol is palmitic acid. The specilicity of cytosolic multienzyme, single-protein fatty acid synthetase is such that once the C16 chain length is reached, a thioesterase clips off the fatty acid. Elongation as well as desaturation of de novo palmitate and fatty acids obtained from the diet occur by the action of enzymes in the membranes of the endoplasmic reticulum. 

Fatty acid elongation mainly occurs in the endoplasmic reticulum where elongases add two carbons to acyl-CoA substrates by using malonyl-CoA. Elongases are the rate-limiting protein acting in a multi proteic complex including a... 

Fatty acid oxidation Acetyl-CoA production Ketone body synthesis Fatty acid elongation... 

Fig. 2. Contribution of the three ketoacyl synthases (KASI, II, and III) to fatty acid elongation. Each circle represents one round of the elongation cycle catalyzed by ketoacyl-ACP synthase, enoyl-ACP reductase, hydroxyacyl-ACP dehydrase, and acyl-ACP reductase.

The predominant pathway for fatty acid elongation occurs in the ER and uses malonyl-CoA and fatty acyl-CoAs as substrates for addition of two carbon atoms to the existing... 

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