Saturated fatty acids elongates

Certain long-chain unsaturated fatty acids of metabolic significance in mammals are shown in Figure 23-1. Other C20, C22, and C24 polyenoic fatty acids may be derived from oleic, linoleic, and a-flnolenic acids by chain elongation. Palmitoleic and oleic acids are not essential in the diet because the tissues can introduce a double bond at the position of a saturated fatty acid. 

The end-product of this process is the C-16 saturated fatty acid, palmitate. The elongation of palmitate to longer-chain fatty acids involves another system (see below). 

As the name anaerobic implies, the double bond of the fatty acid is inserted in the absence of oxygen. Biosynthesis of monounsaturated fatty acids follows the pathway described previously for saturated fatty acids until the intermediate /3-hydroxydecanoyl-ACP is reached (fig. 18.15). At this point, a new enzyme, /3-hydroxydecanoyl-ACP dehydrase, becomes involved. This dehydrase can form the a-j8 trans double bond, and saturated fatty acid synthesis can occur as previously discussed. In addition, this dehydrase is capable of isomerization of the double bond to a cis /3-y double bond as shown in figure 18.15. The /3-y unsaturated fatty acyl-ACP is subsequently elongated by the normal enzymes of fatty acid synthesis to yield pal-mitoleoyl-ACP (16 1A9). The conversion of this compound to the major unsaturated fatty acid of E. coli, cA-vacccnic acid (18 1A11), requires a condensing enzyme that we have not previously discussed, /3-ketoacyl-ACP synthase II, which shows a preference for palmitoleoyl-ACP as a substrate. The subsequent conversion to vaccenyl-ACP is cata-... 

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. 

Saturated fatty acids or unsaturated fatty acids, such as oleic acid (18 1, n-9), can be synthesized by normal mammalian cells that posses elongation and desaturation enzymes (Rosenthal, 1987). However, the polyunsaturated fatty acids of the n-3 and n-6 group, such as linoleic acid (18 2, n-6) or linolenic acid (18 3, n-3), are essential nutrients for animals because they are precursors for the synthesis of eicosanoid hormones such as prostaglandins (Needleman et al., 1986). 

Figure 1.8 shows the synthesis of fatty acids. This complex process is catalysed by the multienzymatic complex, fatty acid synthetase. This enzyme uses as substrates acetyl-coA and malonyl-coA to produce palmitic acid. Afterwards, palmitic acid, a saturated fatty acid of 16 carbon atoms, can be used to produce other fatty acids (Ratledge and Evans 1989). Fatty acids with more carbon units, such as estearic acid, are obtained by elongation of palmitic acid. 

Intestinal Handling of FFA In the cells of the small intestine, several enzymes can act on free but not on esterified fatty acids. In contrast to MAGs, FFA are diluted with fatty acids originating from the plasma free fatty acid pool (44). After activation they can be oxidized, elongated, chain desaturated, and converted into complex lipids (45, 46). The relative rates depend on the nature of the fatty acids and on the presence of other components in the intestinal cells (47). Conversion of saturated fatty acids in monounsaturated ones when they are absorbed as FFA, i.e., when they were present in the outer position of the dietary TAGs, could... 

Fig. 2.13 Biosynthesis of saturated fatty acids in plants and animals. Palmitate is formed by successive additions of malonyl coenzyme A to the enzyme-bound chain, with C02 being lost at each addition.This results in chain elongation by a (CH2)2 unit at each step. Details of the formation of butyryl (C4) from acetyl (C2) are shown, while the subsequent six further additions, terminating in palmitate, proceed similarly.

There is increasing evidence that in plant tissues the synthesis of palmitic acid, the most abundant and important saturated fatty acid in higher plants, involves at/e novo system, so called because it utilizes acetyl-CoA, malonyl-CoA, acyl carrier protein (ACP), and a battery of soluble, nonassociated enzymes (palmitoyl-ACP synthetase) to form, as its terminal product, palmi-toyl-ACP. Palmitoyl-ACP is then elongated by another set of enzymes called... 

Striking are the differences between the components necessary for acyl-CoA elongation according to the organelle in mitochondria acetyl-CoA is the immediate precursor of the two carbon elongation unit and both NADH and NADPH are necessary for synthesis of saturated fatty acids. On the contrary, microsomal enzymes require... 

It appears that dc novo synthesis of saturated fatty acids in the endoplasmic reticulum is not strongly inhibited by fatty acids and acyl CoA s whereas the formation of these acids in the mitochondria, probably by elongation, is completely inhibited under these conditions. Thus the appearance of elongation products in the mitochondria in a mixed incubation may very well involve a transfer process. In order to test this probability, microsomes and mitochondria were incubated separately under optimal conditions with radioactive malonyl or acetyl CoA and in the presence or absence of linoleate. They were then washed free of precursors, and the unincubated particles were added, followed by incubation, separation, and fatty acid and lipid analysis. It can be seen in Tables 3 and 4 that there is very rapid exchange of elongation products in both directions despite the absence of the cytosol which presumably contains... 

Fig. 7. Elongation of endogenous saturated fatty acids in microsomes plus mitochondria. The incubation mixture contained 30 mymoles malonyl CoA, 10 mymoles acetyl CoA, 8 ymoles ATP, 1 ymole NADH,...

---